Due to its constant pumping and contraction, the heart requires a substantial amount of energy, with fatty acids (FAs) providing a major part of its adenosine triphosphate (ATP). However, the heart is incapable of mak...Due to its constant pumping and contraction, the heart requires a substantial amount of energy, with fatty acids (FAs) providing a major part of its adenosine triphosphate (ATP). However, the heart is incapable of making this substrate and attains its FAs from multiple sources, including the action of lipoprotein lipase (LPL). LPL is produced in cardiomyocytes and subsequently secreted to its heparan sulfate proteoglycan (HSPG) binding sites on the plasma membrane. To then move LPL to the endothelial cell (EC) lumen, glycosylphosphatidylinositol-anchored high-density lipoprotein-binding protein 1 (GPIHBP1) attaches to interstitial LPL and transfers it to the vascular lumen, where the LPL is ready to perform its function of breaking down circulating triglycerides (TG) into FAs. The endo-β-glucuronidase heparanase (Hpa) is unique in that it is the only known mammalian enzyme to cleave heparan sulfate (HS), thereby promoting the abovementioned release of LPL from the cardiomyocyte HSPG. In diabetes, it has been suggested that changes in how the heart generates energy are responsible for the development of diabetic cardiomyopathy (DCM). Following moderate diabetes, with the reduction in glucose utilization, the heart increases its LPL activity at the vascular lumen due to an increase in Hpa action. Although this adaptation might be beneficial to compensate for the underutilization of glucose by the heart, it is toxic over the long term, as harmful lipid metabolite accumulation, along with augmented FA oxidation and thus oxidative stress, leads to cell death. This coincides with the loss of a cardioprotective growth factor—namely, vascular endothelial growth factor B (VEGFB). This review discusses interconnections between Hpa, LPL, and VEGFB and their potential implications in DCM. Given that mechanism-based therapeutic care for DCM is unavailable, understanding the pathology of this cardiomyopathy, along with the contribution of LPL, will help us advance its clinical management.展开更多
BACKGROUND The results of previous animal experiments and clinical studies have shown that there is a correlation between expression of betatrophin and blood lipid levels.However,there are still differences studies on...BACKGROUND The results of previous animal experiments and clinical studies have shown that there is a correlation between expression of betatrophin and blood lipid levels.However,there are still differences studies on the correlation and interaction mechanism between betatrophin,angiogenin-likeprotein3(ANGPTL3)and lipoprotein lipase(LPL).In our previous studies,we found an increase in serum ANGPTL3 Levels in Chinese patients with coronary heart disease(CHD).Therefore,we retrospectively studied Kazakh CHD patients.AIM To explore the correlation between the betatrophin/ANGPTL3/LPL pathway and severity of coronary artery disease(CAD)in patients with CHD.METHODS Nondiabetic patients diagnosed with CHD were selected as the case group;79 were of Kazakh descent and 72 were of Han descent.The control groups comprised of 61 Kazakh and 65 Han individuals.The serum levels of betatrophin and LPL were detected by enzyme-linked immunosorbent assay(ELISA),and the double antibody sandwich ELISA was used to detect serum level of ANGPTL3.The levels of triglycerides,total cholesterol,and fasting blood glucose in each group were determined by an automatic biochemical analyzer.At the same time,the clinical baseline data of patients in each group were included.RESULTS Betatrophin,ANGPTL3 and LPL levels of Kazakh patients were significantly higher than those of Han patients(P=0.031,0.038,0.021 respectively).There was a positive correlation between the Gensini score and total cholesterol(TC),triglycerides(TG),low-density lipoprotein cholesterol(LDL-C),betatrophin,and LPL in Kazakh patients(r=0.204,0.453,0.352,0.471,and 0.382 respectively),(P=0.043,0.009,0.048,0.001,and P<0.001 respectively).A positive correlation was found between the Gensini score and body mass index(BMI),TC,TG,LDL-C,LPL,betatrophin in Han patients(r=0.438,0.195,0.296,0.357,0.328,and 0.446 respectively),(P=0.044,0.026,0.003,0.20,0.004,and P<0.001).TG and betatrophin were the risk factors of coronary artery disease in Kazakh patients,while BMI and betatrophin were the risk factors in Han patients.CONCLUSION There was a correlation between the betatrophin/ANGPTL3/LPL pathway and severity of CAD in patients with CHD.展开更多
Objective To study the effects of Hind Ⅲ DNA polymorphism in the lipoprotein lipase (LPL)gene on plasma lipid levels, body mass index (BMI) and subcutaneous fat distribution in simple obesity children.Methods The LPL...Objective To study the effects of Hind Ⅲ DNA polymorphism in the lipoprotein lipase (LPL)gene on plasma lipid levels, body mass index (BMI) and subcutaneous fat distribution in simple obesity children.Methods The LPL Hind Ⅲ genotypes were detected with the polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) techniques in 92 children with simple obesity. The levels of the plasma lipid, plasma lipoproteins, BMI and skinfold thickness in three regions (biceps, subscapular and abdominal wall) were also measured. Results It was shown that the levels of TG, TC, LDL C, ApoB, BMI, biceps and subscapular skinfold thickness, and the average value of the skinfold thickness in three regions were significantly higher in the obese children with H+H+ genotype than those with H+H-genotype. Conclusions It can be concluded that LPL Hind Ⅲ polymorphism may modify the levels of plasma lipid, plasma lipoprotein and BMI in children with simple obesity, and meanwhile alters the distribution of subcutaneous fat.展开更多
Purpose: The purpose of this study was to investigate the relationship between serum levels of lipoprotein lipase(LPL), hepatic lipase(HL), and endothelial lipase(EL) and the progression of coronary artery disease(CAD...Purpose: The purpose of this study was to investigate the relationship between serum levels of lipoprotein lipase(LPL), hepatic lipase(HL), and endothelial lipase(EL) and the progression of coronary artery disease(CAD).Materials and methods: According to the inclusion criteria, exclusion criteria, diagnostic criteria, angiography results, and the random matching scheme, the enrolled patients were divided into the following two groups: the progression-free group(n ? 47) and the progression group(n ? 15). The baseline characteristics and various biochemical parameters were obtained from the medical records and medical history. Serum LPL, HL, and EL levels were detected by ELISA. The correlation between serum LPL, HL, and EL levels and coronary lesions was statistically analyzed with SPSS software.Results: Significant differences were observed in serum levels of HL and EL between the progression-free group and the progression group(HL, 75.5 ? 39.2 ng/mL vs. 125.1 ? 42.1 ng/mL, P < 0.05;EL, 139.2 ? 59.6 pg/mL vs.175.1 ? 40.1 pg/mL, P < 0.05), while the difference in the LPL level was not significant(P > 0.05). Receiver operating characteristic curve(ROC) analysis showed that the area under the curve(AUC) values of LPL, HL, and EL were 0.506(95% CI: 0.369–0.642, P ? 0.9470), 0.792(95% CI: 0.664–0.888, P < 0.0001), and 0.693(95% CI:0.553–0.811, P ? 0.0095), respectively. Additionally, logistic regression analysis showed that the serum level of HL was an independent risk factor for coronary artery lesion progression.Conclusion: Serum levels of EL and HL, but not the serum level of LPL, were positively correlated with the progression of CAD. The serum level of HL was an independent risk factor for the progression of CAD, while the serum level of EL or LPL was not an independent risk factor for the progression of CAD. For the diagnosis of CAD progression, the serum level of HL was better than the serum level of EL or LPL.展开更多
This study demonstrated that homogenization did not increase the activity of lipoprotein lipase (LPL) in spite of a fast accumulation of free fatty acids (FFA). Two homogenization pressures (100 and 170 bar) and two t...This study demonstrated that homogenization did not increase the activity of lipoprotein lipase (LPL) in spite of a fast accumulation of free fatty acids (FFA). Two homogenization pressures (100 and 170 bar) and two temperatures (40℃and 50℃) were examined. The activity of LPL was analyzed and the formation of FFA was measured with two different methods, the B.D.I.-method and a nonesterified fatty acids (NEFA) method. A homogenization temperature of 50℃ resulted in a decreased LPL activity compared to 40℃. No effect of homogenization pressure was found. Analyzing FFA concentration with the B.D.I.-method resulted in significant effect of homogenization temperature and no effect of pressure. The largest formation of FFA was found in milk homogenized at 40℃. Using the NEFA method, another result was obtained, indicating no effect of homogenization temperature and a larger FFA accumulation at 100 bar than at 170 bar. Both analytic methods demonstrated significant production of FFA during 60 min incubation at homogenization temperature after treatment. The level of FFA in the milk samples immediately after homogenization was very high, demonstrating that LPL cleaves the triglycerides very rapidly when the native membrane was damaged. The regression between the B.D.I.-method and the NEFA was fair in the interval between 4 and 14 mmol/100 g fat, whereas at higher concentrations, the correlation was poor.展开更多
AIM: To examine the influence of lipoprotein lipase (LPL) gene polymorphism in ulcerative colitis (UC) patients. METHODS: Peripheral blood was obtained from 131 pa- tients with UC and 106 healthy controls for DNA extr...AIM: To examine the influence of lipoprotein lipase (LPL) gene polymorphism in ulcerative colitis (UC) patients. METHODS: Peripheral blood was obtained from 131 pa- tients with UC and 106 healthy controls for DNA extrac- tion. We determined LPL gene polymorphisms affecting the enzyme at Ser447stop, as well as HindⅢ and Pvu Ⅱ polymorphisms using PCR techniques. PCR products were characterized by PCR-RFLP and direct sequencing. Polymorphisms were examined for association with clini- cal features in UC patients. Genotype frequencies for LPL polymorphisms were also compared between UC patients and controls. RESULTS: In patients with onset at age 20 years or younger, C/G and G/G genotypes for Ser447stop poly- morphism were more prevalent than C/C genotype (OR = 3.13, 95% CI = 0.95-10.33). Patients with H+/- or H-/-genotype for HindⅢ polymorphism also were more nu- merous than those with H+/+ genotype (OR = 2.51, 95% CI = 0.85-7.45). In the group with H+/+ genotype for HindⅢ polymorphism, more patients had serum triglyc- eride concentrations over 150 mg/dL than patients with H+/- or H-/- genotype (P < 0.01, OR = 6.46, 95% CI = 1.39-30.12). Hypertriglycemia was also more prevalent in patients with P+/+ genotypes for PvuⅡ polymorphism (P < 0.05, OR = 3.0, 95% CI = 1.06-8.50). Genotype fre- quency for LPL polymorphism did not differ significantly between UC patients and controls. CONCLUSION: Ser447stop and HindⅢ LPL polymor- phisms may influence age of onset of UC, while HindⅢ and PvuⅡ polymorphisms influence serum triglyceride in UC patients.展开更多
Porcine lipoprotein lipase (LPL) cDNA was cloned as the standard for real-time quantifying LPL mRNA and the TaqMan-fluorescence quantitative PCR assay for detection was established. The total RNA extracted from Longis...Porcine lipoprotein lipase (LPL) cDNA was cloned as the standard for real-time quantifying LPL mRNA and the TaqMan-fluorescence quantitative PCR assay for detection was established. The total RNA extracted from Longissimus dorsi of porcine was reverse-transcribed to cDNA. LPL cDNA was ligated with pGM-T vector and transformed into Escherichia coli TOP10. Plasmid DNA extracted from positive clones was verified by PCR amplification and sequenced. LPL was amplified by real-time fluorescence quantitative PCR from the plasmid DNA. The concentration of DNA template purified was detected by analyzing absorbance in 260 nm and then the combined plasmid was diluted to series as standard for fluorescence quantitative PCR (FQ-PCR). The method of LPL mRNA real-time PCR was well established, which detected as low as 103 with the linear range 103 to 1010 copies. The standard curves showed high correlations (R2 = 0.9871). A series of standards for real-time PCR analysis have been constructed successfully, and real-time TaqMan-fluorescence quantitative RT-PCR is reliable to quantitatively evaluate FQ-PCR mRNA in L. dorsi of porcine.展开更多
OBJECTIVE Normal male aging is associated with declines in levels of the sex steroid hormone testosterone. A large body of evidence supports a neurotrophic role for testosterone in central nervous system. Lipoprotein ...OBJECTIVE Normal male aging is associated with declines in levels of the sex steroid hormone testosterone. A large body of evidence supports a neurotrophic role for testosterone in central nervous system. Lipoprotein lipase(LPL) is also expressed in the brain with highest levels found in the pyramidal cells of the hippocampus, we previous reported LPL-deficient mice exhibited memory disfunction. Testosterone is known to be largely converted to estradiol following aromatization within the hippocampus. Although testosterone has been implicated in lipid metabolism, it remains elusive whether testosterone can regulate brain LPL through DNA methylation mechanism. In order to clarify DNA methylation control exerted by testosterone over LPL gene in central nervous system, and its effect on lipid metabolism, we examined the adult male rat hippocampus to determine whether castration induced testosterone deficiency can affect lipid profile and LPL gene expression through its altered methylation pattern. METHODS Model of aging with declines in levels of the sex steroid hormone testosterone was performed as our previous description. RESULTS(1) Serum testosterone and brain testosterone levels were significantly decreased, which were restored to the control level after testosterone replacement,respectively(P<0.01);(2) Androgen deficiency was not found in Morris water maze and motor performance, however, androgen deficiency increases neurological and cognitive impairment in aged rats.(3)Decreased expression of olfactory marker protein(OMP) in olfactory bulb of SD rats treated with androgen deficiency.(4) The expression of Fox O3 and OMP in the olfactory bulb of androgen deficient rats was down-regulated, accompanied by dysfunction of the olfactory limbic system.(5) Decreased LPL m RNA level and inversely increased LPL promoter methylation level were observed following androgen deficiency and reserved by testosterone replacement.(6) In contrast, androgen deficiency slightly increased estrogen receptor beta(ERβ) m RNA levels and significantly decreased its promoter methylation levels within the hippocampus, and reserved as well by testosterone replacement. CONCLUSION(1) LPL in synaptic plasticity and contributes to a better understanding of the LPL function in the brain, where altered LPL levels are related to learning and memory impairment.(2) Androgen and Fox O3 play an important role in the olfactory cognitive process of the nervous system.(3) LPL expression in hippocampus is actively maintained by sex steroid hormones and that DNA methylation modification may contribute to this homeostatic regulation.展开更多
Obesity is one of the fast-growing major diseases in developed and developing countries. As has been persuasively argued, long-term imbalance between intake and expenditure of fat is a central factor in the etiology o...Obesity is one of the fast-growing major diseases in developed and developing countries. As has been persuasively argued, long-term imbalance between intake and expenditure of fat is a central factor in the etiology of obesity. Obesity aggravates insulin resistance and promotes cardiovascular diseases and atherosclerosis. We hypothesized that elevating lipoprOtein lipase (LPL) activity in skeletal muscle would cause an improvement of obesity. To test this hypothesis, we studied the effects of the LPL activator NO-1886 inobese animals. NO-1886 elevated LPL activity in skeletal muscle, and improved obesity as well as insulin resistance in obese rats. Furthermore, NO-1886 mitigated body weight gain induced by pioglitazone without suppressive effect on the adiponectin-increasing action of pioglitazone. LPL activators hold a lot of promise of curing several diseases shown above in clinical scene.展开更多
In mammals,lipoprotein lipase(LPL)has been found to play an important role in lipid mentalismand deposition.LPL deficiency in humans(Homo sapiens)and mice(Mus musculus)tends to cause hypertriglyceridemia.The lpl gene ...In mammals,lipoprotein lipase(LPL)has been found to play an important role in lipid mentalismand deposition.LPL deficiency in humans(Homo sapiens)and mice(Mus musculus)tends to cause hypertriglyceridemia.The lpl gene is not expressed in adult mammalian liver,but is in adult fish liver.The functions provided by the lpl gene are diverse in vertebrates.Here,we knocked out the lpl gene in Japanese medaka(Oryzias latipes)with the CRISPR/Cas9 system.The lpl-knockout(KO)homozygous individuals showed severe developmental defects with an extremely emaciated and deformedbody and onlyaccounted for about5%of the F2fish.This is consistentwiththefindings inmicebut disaccords with the results for zebrafish(Danio rerio).Compared with wild-type(WT)madaka,the mRNA level of lpl in lpl-KO heterozygous mutant was significantly higher in the muscle,showed no significant difference in the liver,and was significantly lower in the heart.Under lpl heterozygous deficiency,the relative area of Oil RedO and triglycerides(TG)level in the liver,heart and muscle tissue covaried with levels of lpl mRNA in medaka.The lpl heterozygous deficiency did not affect the levelsofTG,low-density lipoprotein cholesterol(LDL-C),high-density lipoprotein cholesterol(HDL-C)and total cholesterol(TC)in the plasma of medaka,which is inconsistent with the findings in mammals.In general,the lpl gene plays an important role in the growth and development and is closely related to lipid deposition of medaka.展开更多
Objective:To investigate the anti-hyperlipidemic effects of apple polyphenols extract(APE)in Triton WR-1339-induced endogenous hyperlipidemic model.Methods:Firstly,APE was isolated and purified from the pomace of Red ...Objective:To investigate the anti-hyperlipidemic effects of apple polyphenols extract(APE)in Triton WR-1339-induced endogenous hyperlipidemic model.Methods:Firstly,APE was isolated and purified from the pomace of Red Fuji Apple and contents of individual polyphenols in APE were determined using highperformance liquid chromatography-mass spectrometry(HPLC-MS).Secondly,forty male National Institude of Health(NIH)mice were randomly divided into 5 groups with 8 animals in each group.The Fenofibrate Capsules(FC)group and APE groups received oral administration of respective drugs for 7 consecutive days.All mice except those in the normal group were intravenously injected through tail vein with Triton WR-1339 on the6th day.Serum and livers from all the mice were obtained 18 h after the injection.The changes in serum total cholesterol(TC),triglyceride(TG),lipoprotein lipase(LPL)and hepatic triglyceride lipase(HTGL)were measured by respective kits.Finally,expression of hepatic peroxisome proliferator-activated receptor alpha(PPARα)mRNA was measured by real-time reverse transcription-polymerase chain reaction(RT-PCR)method.Results:Serum TC and TG levels significantly increased in Triton WR-1339-induced model group compared with the normal group(P<0.01).Oral administration of APE[200 and 400 mg/(kg·day)]dose-dependently reduced the serum level of TG in hyperlipidemic mice(P<0.01).Serum LPL and HTGL activities significantly decreased in Triton WR-1339-induced model group compared with the normal group(P<0.05).Oral administration of APE[200 and 400 mg/(kg·day)]dose-dependently elevated the serum activity of LPL in hyperlipidemic mice(P<0.05or P<0.01).Furthermore,compared with the normal group,hepatic mRNA level of PPARαin the model group significantly decreased(P<0.01).Oral administration of APE[200 and 400 mg/(kg·day)]dose-dependently elevated the expression of PPARαin hyperlipidemic mice(P<0.05 or P<0.01).Conclusion:APE could reduce TG level via up-regulation of LPL activity,which provides new evidence to elucidate the anti-hyperlipidemic effects of APE.展开更多
Atherosclerosis manifests itself clinically at advanced stages when plaques undergo hemorrhage and/or rupture with superimposed thrombosis, thus abruptly stopping blood supply. Identification of markers of plaque dest...Atherosclerosis manifests itself clinically at advanced stages when plaques undergo hemorrhage and/or rupture with superimposed thrombosis, thus abruptly stopping blood supply. Identification of markers of plaque destabilization at a pre-clinical stage is, therefore, a major goal of cardiovascular research. Promising results along this line were provided by studies investigating the lipoprotein-associated phospholipase A2(Lp-PLA2), a member of phospholipase A2 proteins family that plays a key role in the metabolism of pro-inflammatory phospholipids, as oxidized low-density lipoproteins, and in the generation of pro-atherogenic metabolites, including lysophosphatidylcholine and oxidized free fatty acids. We herein review the experimental and clinical studies supporting use of Lp-PLA2 activity for predicting cardiovascular events. To his end we considered not only Lp-PLA2 activity and mass, but also Lp-PLA2 gene variations and their association with incident coronary artery disease, stroke, and cardiovascular mortality. Based on these evidences the major scientific societies have included in their guidelines the measurement of Lp-PLA2 activity among the biomarkers that are useful in risk stratification of adult asymptomatic patients at intermediate cardiovascular risk. The results of two recently published major clinical trials with the LpPLA2 inhibitor darapladib, which seem to challenge the pathogenic role of Lp-PLA2, will also be discussed.展开更多
Lipoprotein(a) [Lp(a)] is composed of a low density lipoprotein(LDL)-like particle to which apolipoprotein(a)[apo(a)] is linked by a single disulfide bridge. Lp(a) is considered a causal risk factor for ischemic cardi...Lipoprotein(a) [Lp(a)] is composed of a low density lipoprotein(LDL)-like particle to which apolipoprotein(a)[apo(a)] is linked by a single disulfide bridge. Lp(a) is considered a causal risk factor for ischemic cardiovascular disease(CVD) and calcific aortic valve stenosis(CAVS). The evidence for a causal role of Lp(a) in CVD and CAVS is based on data from large epidemiological databases, mendelian randomization studies, and genome-wide association studies. Despite the well-established role of Lp(a) as a causal risk factor for CVD and CAVS, the underlying mechanisms are not well understood. A key role in the Lp(a) functionality may be played by its oxidized phospholipids(OxPL) content. Importantly, most of circulating OxPL are associated with Lp(a); however, the underlying mechanisms leading to this preferential sequestration of OxPL on Lp(a) over the other lipoproteins,are mostly unknown. Several studies support the hypothesis that the risk of Lp(a) is primarily driven by its OxPL content.An important role in Lp(a) functionality may be played by the lipoprotein-associated phospholipase A_2(Lp-PLA_2),an enzyme that catalyzes the degradation of OxPL and is bound to plasma lipoproteins including Lp(a). The present review article discusses new data on the pathophysiological role of Lp(a) and particularly focuses on the functional role of OxPL and Lp-PLA_2 associated with Lp(a).展开更多
Objective: To investigate the mechanism of Astragalus-Angelica Mixture (AAM)’s effects on lipid metabolism disturbance in nephrotic rats.Methods: To examine the effects of AAM on serum albumin, lipid levels, and acti...Objective: To investigate the mechanism of Astragalus-Angelica Mixture (AAM)’s effects on lipid metabolism disturbance in nephrotic rats.Methods: To examine the effects of AAM on serum albumin, lipid levels, and activities of lipoprotein lipase (LPL) and lecithin-cholesterol acyltransferase (LCAT), which are key enzymes for metabolism of lipid in immune-induced nephrotic hyperlipidemia rats and exogenous hyperlipidemia rats.Results: In nephrotic rats, serum albumin was reduced, lipid increased significantly, LPL activity decreased markedly and the LCAT activity was relatively insufficient. Activities of LPL and LCAT increased obviously in AAM treated nephrotic rats. There were no change of activities of LPL and LCAT in exogenous hyperlipidemia rats and AAM showed no effect on the activities of these two enzymes. Conclusion: The effect of AAM on regulating lipid metabolism might be due to enhance the clearance of both triglyceride-rich and cholesterol-rich apoB containing lipoprotein by improving the activities of LPL and LCAT.展开更多
Objective:To evaluate the influence of–250G>A(rs2070895)polymorphism in hepatic lipase gene(LIPC)promoter on plasma lipid parameters of ischemic stroke patients.Methods:A total of 100 stroke patients and 100 contr...Objective:To evaluate the influence of–250G>A(rs2070895)polymorphism in hepatic lipase gene(LIPC)promoter on plasma lipid parameters of ischemic stroke patients.Methods:A total of 100 stroke patients and 100 control subjects matched for sex(59 men and 41 women)and age were selected.Hepatic lipase activity and lipid profiles were measured while lipoprotein ratios were calculated.Genotyping of the–250G>A promoter polymorphism of the LIPC was performed by the polymerase chain reaction and restriction fragment length polymorphism method combined with 2%gel electrophoresis and then confirmed by direct sequencing.The LIPC promoter gene sequencing data were compared with refseqNG011465.1 LIPC from GenBank.Results:The frequencies of GG,GA and AA genotypes of LIPC rs2070895 polymorphism were 39%,45%and 16%for the control,10%,37%and 53%for the stroke subjects(P<0.0001),respectively.The frequencies of G and A alleles were 61.5%and 38.5%for the control,and 28.5%and 71.5%for the stroke subjects(P<0.0001).Our study shows that the mutant allele of the LIPC promoter was associated with dyslipidemia,lower hepatic lipase activity,and this variation contributed to the increased defective plasma high-density lipoprotein-cholesterol(HDL-C),HDL2-C and HDL3-C concentration for both subjects.The control subjects had 6 single nucleotide polymorphism and 6 amino acid substitutions while the stroke subjects had 32 single nucleotide polymorphism and 20 amino acid substitutions.Conclusions:LIPC–250G>A polymorphism can influence plasma lipid profiles and lipoprotein ratios in patients with ischemic stroke.展开更多
Diabetic dyslipidemia is characterized by quantitative and qualitative abnormalities in lipoproteins.In addition to glycation and oxidation,carbamylation is also a post-translational modification affecting lipoprotein...Diabetic dyslipidemia is characterized by quantitative and qualitative abnormalities in lipoproteins.In addition to glycation and oxidation,carbamylation is also a post-translational modification affecting lipoproteins in diabetes.Patients with type 2 diabetes(T2D)exhibit higher levels of carbamylated low-density lipoproteins(cLDL)and high-density lipoproteins(cHDL).Accumulating evidence suggests that cLDL plays a role in atherosclerosis in diabetes.cLDL levels have been shown to predict cardiovascular events and all-cause mortality.cLDL facilitates immune cell recruitment in the vascular wall,promotes accumulation of lipids in macrophages,and contributes to endothelial dysf-unction,endothelial nitric oxide-synthase(eNOS)inactivation and endothelial repair defects.Lastly,cLDL induces thrombus formation and platelet aggregation.On the other hand,recent data have demonstrated that cHDL serum level is independently associated with all-cause and cardiovascular-related mortality in T2D patients.This relationship may be causative since the atheroprotective properties of HDL are altered after carbamylation.Thus,cHDL loses the ability to remove cholesterol from macrophages,to inhibit monocyte adhesion and recruitment,to induce eNOS activation and to inhibit apoptosis.Taken together,it seems very likely that the abnormalities in the biological functions of LDL and HDL after carbamylation contribute to atherosclerosis and to the elevated cardiovascular risk in diabetes.展开更多
Objective To explore the relationship between the lipoprotein lipase(LPL)-447C/G gene polymorphism and cerebral infarction in the elderly. Methods This was a case-control study,which enrolled 206 cases with cerebral i...Objective To explore the relationship between the lipoprotein lipase(LPL)-447C/G gene polymorphism and cerebral infarction in the elderly. Methods This was a case-control study,which enrolled 206 cases with cerebral infarction in the elderly and 203展开更多
We described a novel polymer-lipase conjugate for high-efficient esterification of vitamin E using vitamin E and succinic anhydride as the substrates in nonaqueous media.In this work,the monomer,N-isopropylacrylamide(...We described a novel polymer-lipase conjugate for high-efficient esterification of vitamin E using vitamin E and succinic anhydride as the substrates in nonaqueous media.In this work,the monomer,N-isopropylacrylamide(NIPAM),was grafted onto Candida rugosa lipase(CRL)to synthesize poly(NIPAM)(pNIPAM)-CRL conjugate by atom transfer radical polymerization via the initiator coupled on the surface of CRL.The result showed that the catalytic efficiencies of pNIPAM-CRL conjugates(19.5-30.3 L·s^(-1)·mmol^(-1))were at least 7 times higher than that of free CRL(2.36 L·s^(-1)·mmol^(-1))in DMSO.It was attributed to a significant increase in Kcat of the conjugates in nonaqueous media.The synthesis catalyzed by pNIPAM-CRL co njugates was influenced by the length and density of the grafted polymer,water content,solvent polarity and molar ratio of the substrates.In the optimal synthesis,the reaction time was shortened at least 7 times,and yields of vitamin E succinate by pNIPAM-g-CRL and free CRL were obtained to be 75.4%and 6.6%at 55℃after the reaction for 1.5 h.The result argued that conjugation with pNIPAM induced conformational change of the lid on CRL based on hydrophobic interaction,thus providing a higher possibility of catalysis-favorable conformation on CRL in nonaqueous media.Moreover,pNIPAM conjugation improved the thermal stability of CRL greatly,and the stability improved further with an increase of chain length of pNIPAM.At the optimal reaction conditions(55℃and 1.5 h),pNIPAM-g-CRL also exhibited good reusability in the enzymatic synthesis of vitamin E succinate and kept~70%of its catalytic activity after ten consecutive cycles.The research demonstrated that pNIPAM-g-CRL was a more competitive biocatalyst in the enzymatic synthesis of vitamin E succinate and exhibited good application potential under harsh industrial conditions.展开更多
基金supported by operating grants from the Canadian Institutes of Health Research(CIHR PJT-178134 and PJT-169212).
文摘Due to its constant pumping and contraction, the heart requires a substantial amount of energy, with fatty acids (FAs) providing a major part of its adenosine triphosphate (ATP). However, the heart is incapable of making this substrate and attains its FAs from multiple sources, including the action of lipoprotein lipase (LPL). LPL is produced in cardiomyocytes and subsequently secreted to its heparan sulfate proteoglycan (HSPG) binding sites on the plasma membrane. To then move LPL to the endothelial cell (EC) lumen, glycosylphosphatidylinositol-anchored high-density lipoprotein-binding protein 1 (GPIHBP1) attaches to interstitial LPL and transfers it to the vascular lumen, where the LPL is ready to perform its function of breaking down circulating triglycerides (TG) into FAs. The endo-β-glucuronidase heparanase (Hpa) is unique in that it is the only known mammalian enzyme to cleave heparan sulfate (HS), thereby promoting the abovementioned release of LPL from the cardiomyocyte HSPG. In diabetes, it has been suggested that changes in how the heart generates energy are responsible for the development of diabetic cardiomyopathy (DCM). Following moderate diabetes, with the reduction in glucose utilization, the heart increases its LPL activity at the vascular lumen due to an increase in Hpa action. Although this adaptation might be beneficial to compensate for the underutilization of glucose by the heart, it is toxic over the long term, as harmful lipid metabolite accumulation, along with augmented FA oxidation and thus oxidative stress, leads to cell death. This coincides with the loss of a cardioprotective growth factor—namely, vascular endothelial growth factor B (VEGFB). This review discusses interconnections between Hpa, LPL, and VEGFB and their potential implications in DCM. Given that mechanism-based therapeutic care for DCM is unavailable, understanding the pathology of this cardiomyopathy, along with the contribution of LPL, will help us advance its clinical management.
基金Supported by National Natural Science Foundation of China,No.8660085Natural Science Foundation of Shihezi University,No.ZZZC201712A
文摘BACKGROUND The results of previous animal experiments and clinical studies have shown that there is a correlation between expression of betatrophin and blood lipid levels.However,there are still differences studies on the correlation and interaction mechanism between betatrophin,angiogenin-likeprotein3(ANGPTL3)and lipoprotein lipase(LPL).In our previous studies,we found an increase in serum ANGPTL3 Levels in Chinese patients with coronary heart disease(CHD).Therefore,we retrospectively studied Kazakh CHD patients.AIM To explore the correlation between the betatrophin/ANGPTL3/LPL pathway and severity of coronary artery disease(CAD)in patients with CHD.METHODS Nondiabetic patients diagnosed with CHD were selected as the case group;79 were of Kazakh descent and 72 were of Han descent.The control groups comprised of 61 Kazakh and 65 Han individuals.The serum levels of betatrophin and LPL were detected by enzyme-linked immunosorbent assay(ELISA),and the double antibody sandwich ELISA was used to detect serum level of ANGPTL3.The levels of triglycerides,total cholesterol,and fasting blood glucose in each group were determined by an automatic biochemical analyzer.At the same time,the clinical baseline data of patients in each group were included.RESULTS Betatrophin,ANGPTL3 and LPL levels of Kazakh patients were significantly higher than those of Han patients(P=0.031,0.038,0.021 respectively).There was a positive correlation between the Gensini score and total cholesterol(TC),triglycerides(TG),low-density lipoprotein cholesterol(LDL-C),betatrophin,and LPL in Kazakh patients(r=0.204,0.453,0.352,0.471,and 0.382 respectively),(P=0.043,0.009,0.048,0.001,and P<0.001 respectively).A positive correlation was found between the Gensini score and body mass index(BMI),TC,TG,LDL-C,LPL,betatrophin in Han patients(r=0.438,0.195,0.296,0.357,0.328,and 0.446 respectively),(P=0.044,0.026,0.003,0.20,0.004,and P<0.001).TG and betatrophin were the risk factors of coronary artery disease in Kazakh patients,while BMI and betatrophin were the risk factors in Han patients.CONCLUSION There was a correlation between the betatrophin/ANGPTL3/LPL pathway and severity of CAD in patients with CHD.
文摘Objective To study the effects of Hind Ⅲ DNA polymorphism in the lipoprotein lipase (LPL)gene on plasma lipid levels, body mass index (BMI) and subcutaneous fat distribution in simple obesity children.Methods The LPL Hind Ⅲ genotypes were detected with the polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) techniques in 92 children with simple obesity. The levels of the plasma lipid, plasma lipoproteins, BMI and skinfold thickness in three regions (biceps, subscapular and abdominal wall) were also measured. Results It was shown that the levels of TG, TC, LDL C, ApoB, BMI, biceps and subscapular skinfold thickness, and the average value of the skinfold thickness in three regions were significantly higher in the obese children with H+H+ genotype than those with H+H-genotype. Conclusions It can be concluded that LPL Hind Ⅲ polymorphism may modify the levels of plasma lipid, plasma lipoprotein and BMI in children with simple obesity, and meanwhile alters the distribution of subcutaneous fat.
基金supported by grants from the Medical Engineering Cross Research Fund of Shanghai Jiao Tong University (YG2015ZD03)the National Natural Science Foundation of China (81800375)
文摘Purpose: The purpose of this study was to investigate the relationship between serum levels of lipoprotein lipase(LPL), hepatic lipase(HL), and endothelial lipase(EL) and the progression of coronary artery disease(CAD).Materials and methods: According to the inclusion criteria, exclusion criteria, diagnostic criteria, angiography results, and the random matching scheme, the enrolled patients were divided into the following two groups: the progression-free group(n ? 47) and the progression group(n ? 15). The baseline characteristics and various biochemical parameters were obtained from the medical records and medical history. Serum LPL, HL, and EL levels were detected by ELISA. The correlation between serum LPL, HL, and EL levels and coronary lesions was statistically analyzed with SPSS software.Results: Significant differences were observed in serum levels of HL and EL between the progression-free group and the progression group(HL, 75.5 ? 39.2 ng/mL vs. 125.1 ? 42.1 ng/mL, P < 0.05;EL, 139.2 ? 59.6 pg/mL vs.175.1 ? 40.1 pg/mL, P < 0.05), while the difference in the LPL level was not significant(P > 0.05). Receiver operating characteristic curve(ROC) analysis showed that the area under the curve(AUC) values of LPL, HL, and EL were 0.506(95% CI: 0.369–0.642, P ? 0.9470), 0.792(95% CI: 0.664–0.888, P < 0.0001), and 0.693(95% CI:0.553–0.811, P ? 0.0095), respectively. Additionally, logistic regression analysis showed that the serum level of HL was an independent risk factor for coronary artery lesion progression.Conclusion: Serum levels of EL and HL, but not the serum level of LPL, were positively correlated with the progression of CAD. The serum level of HL was an independent risk factor for the progression of CAD, while the serum level of EL or LPL was not an independent risk factor for the progression of CAD. For the diagnosis of CAD progression, the serum level of HL was better than the serum level of EL or LPL.
文摘This study demonstrated that homogenization did not increase the activity of lipoprotein lipase (LPL) in spite of a fast accumulation of free fatty acids (FFA). Two homogenization pressures (100 and 170 bar) and two temperatures (40℃and 50℃) were examined. The activity of LPL was analyzed and the formation of FFA was measured with two different methods, the B.D.I.-method and a nonesterified fatty acids (NEFA) method. A homogenization temperature of 50℃ resulted in a decreased LPL activity compared to 40℃. No effect of homogenization pressure was found. Analyzing FFA concentration with the B.D.I.-method resulted in significant effect of homogenization temperature and no effect of pressure. The largest formation of FFA was found in milk homogenized at 40℃. Using the NEFA method, another result was obtained, indicating no effect of homogenization temperature and a larger FFA accumulation at 100 bar than at 170 bar. Both analytic methods demonstrated significant production of FFA during 60 min incubation at homogenization temperature after treatment. The level of FFA in the milk samples immediately after homogenization was very high, demonstrating that LPL cleaves the triglycerides very rapidly when the native membrane was damaged. The regression between the B.D.I.-method and the NEFA was fair in the interval between 4 and 14 mmol/100 g fat, whereas at higher concentrations, the correlation was poor.
文摘AIM: To examine the influence of lipoprotein lipase (LPL) gene polymorphism in ulcerative colitis (UC) patients. METHODS: Peripheral blood was obtained from 131 pa- tients with UC and 106 healthy controls for DNA extrac- tion. We determined LPL gene polymorphisms affecting the enzyme at Ser447stop, as well as HindⅢ and Pvu Ⅱ polymorphisms using PCR techniques. PCR products were characterized by PCR-RFLP and direct sequencing. Polymorphisms were examined for association with clini- cal features in UC patients. Genotype frequencies for LPL polymorphisms were also compared between UC patients and controls. RESULTS: In patients with onset at age 20 years or younger, C/G and G/G genotypes for Ser447stop poly- morphism were more prevalent than C/C genotype (OR = 3.13, 95% CI = 0.95-10.33). Patients with H+/- or H-/-genotype for HindⅢ polymorphism also were more nu- merous than those with H+/+ genotype (OR = 2.51, 95% CI = 0.85-7.45). In the group with H+/+ genotype for HindⅢ polymorphism, more patients had serum triglyc- eride concentrations over 150 mg/dL than patients with H+/- or H-/- genotype (P < 0.01, OR = 6.46, 95% CI = 1.39-30.12). Hypertriglycemia was also more prevalent in patients with P+/+ genotypes for PvuⅡ polymorphism (P < 0.05, OR = 3.0, 95% CI = 1.06-8.50). Genotype fre- quency for LPL polymorphism did not differ significantly between UC patients and controls. CONCLUSION: Ser447stop and HindⅢ LPL polymor- phisms may influence age of onset of UC, while HindⅢ and PvuⅡ polymorphisms influence serum triglyceride in UC patients.
基金support provided by the 973 Program of China (2004CB117500)
文摘Porcine lipoprotein lipase (LPL) cDNA was cloned as the standard for real-time quantifying LPL mRNA and the TaqMan-fluorescence quantitative PCR assay for detection was established. The total RNA extracted from Longissimus dorsi of porcine was reverse-transcribed to cDNA. LPL cDNA was ligated with pGM-T vector and transformed into Escherichia coli TOP10. Plasmid DNA extracted from positive clones was verified by PCR amplification and sequenced. LPL was amplified by real-time fluorescence quantitative PCR from the plasmid DNA. The concentration of DNA template purified was detected by analyzing absorbance in 260 nm and then the combined plasmid was diluted to series as standard for fluorescence quantitative PCR (FQ-PCR). The method of LPL mRNA real-time PCR was well established, which detected as low as 103 with the linear range 103 to 1010 copies. The standard curves showed high correlations (R2 = 0.9871). A series of standards for real-time PCR analysis have been constructed successfully, and real-time TaqMan-fluorescence quantitative RT-PCR is reliable to quantitatively evaluate FQ-PCR mRNA in L. dorsi of porcine.
基金NBRD Program of China(2016YFC1306302 2016YFC1305903)+3 种基金National Natural Science Foundation of China(81571044 81471633 61450004 and 81171015)
文摘OBJECTIVE Normal male aging is associated with declines in levels of the sex steroid hormone testosterone. A large body of evidence supports a neurotrophic role for testosterone in central nervous system. Lipoprotein lipase(LPL) is also expressed in the brain with highest levels found in the pyramidal cells of the hippocampus, we previous reported LPL-deficient mice exhibited memory disfunction. Testosterone is known to be largely converted to estradiol following aromatization within the hippocampus. Although testosterone has been implicated in lipid metabolism, it remains elusive whether testosterone can regulate brain LPL through DNA methylation mechanism. In order to clarify DNA methylation control exerted by testosterone over LPL gene in central nervous system, and its effect on lipid metabolism, we examined the adult male rat hippocampus to determine whether castration induced testosterone deficiency can affect lipid profile and LPL gene expression through its altered methylation pattern. METHODS Model of aging with declines in levels of the sex steroid hormone testosterone was performed as our previous description. RESULTS(1) Serum testosterone and brain testosterone levels were significantly decreased, which were restored to the control level after testosterone replacement,respectively(P<0.01);(2) Androgen deficiency was not found in Morris water maze and motor performance, however, androgen deficiency increases neurological and cognitive impairment in aged rats.(3)Decreased expression of olfactory marker protein(OMP) in olfactory bulb of SD rats treated with androgen deficiency.(4) The expression of Fox O3 and OMP in the olfactory bulb of androgen deficient rats was down-regulated, accompanied by dysfunction of the olfactory limbic system.(5) Decreased LPL m RNA level and inversely increased LPL promoter methylation level were observed following androgen deficiency and reserved by testosterone replacement.(6) In contrast, androgen deficiency slightly increased estrogen receptor beta(ERβ) m RNA levels and significantly decreased its promoter methylation levels within the hippocampus, and reserved as well by testosterone replacement. CONCLUSION(1) LPL in synaptic plasticity and contributes to a better understanding of the LPL function in the brain, where altered LPL levels are related to learning and memory impairment.(2) Androgen and Fox O3 play an important role in the olfactory cognitive process of the nervous system.(3) LPL expression in hippocampus is actively maintained by sex steroid hormones and that DNA methylation modification may contribute to this homeostatic regulation.
文摘Obesity is one of the fast-growing major diseases in developed and developing countries. As has been persuasively argued, long-term imbalance between intake and expenditure of fat is a central factor in the etiology of obesity. Obesity aggravates insulin resistance and promotes cardiovascular diseases and atherosclerosis. We hypothesized that elevating lipoprOtein lipase (LPL) activity in skeletal muscle would cause an improvement of obesity. To test this hypothesis, we studied the effects of the LPL activator NO-1886 inobese animals. NO-1886 elevated LPL activity in skeletal muscle, and improved obesity as well as insulin resistance in obese rats. Furthermore, NO-1886 mitigated body weight gain induced by pioglitazone without suppressive effect on the adiponectin-increasing action of pioglitazone. LPL activators hold a lot of promise of curing several diseases shown above in clinical scene.
基金the National Natural Science Foundation of China(31972809)China Agriculture Research System(CARS-46)the National Key R&D Program of China(2019YFD0900500).
文摘In mammals,lipoprotein lipase(LPL)has been found to play an important role in lipid mentalismand deposition.LPL deficiency in humans(Homo sapiens)and mice(Mus musculus)tends to cause hypertriglyceridemia.The lpl gene is not expressed in adult mammalian liver,but is in adult fish liver.The functions provided by the lpl gene are diverse in vertebrates.Here,we knocked out the lpl gene in Japanese medaka(Oryzias latipes)with the CRISPR/Cas9 system.The lpl-knockout(KO)homozygous individuals showed severe developmental defects with an extremely emaciated and deformedbody and onlyaccounted for about5%of the F2fish.This is consistentwiththefindings inmicebut disaccords with the results for zebrafish(Danio rerio).Compared with wild-type(WT)madaka,the mRNA level of lpl in lpl-KO heterozygous mutant was significantly higher in the muscle,showed no significant difference in the liver,and was significantly lower in the heart.Under lpl heterozygous deficiency,the relative area of Oil RedO and triglycerides(TG)level in the liver,heart and muscle tissue covaried with levels of lpl mRNA in medaka.The lpl heterozygous deficiency did not affect the levelsofTG,low-density lipoprotein cholesterol(LDL-C),high-density lipoprotein cholesterol(HDL-C)and total cholesterol(TC)in the plasma of medaka,which is inconsistent with the findings in mammals.In general,the lpl gene plays an important role in the growth and development and is closely related to lipid deposition of medaka.
文摘Objective:To investigate the anti-hyperlipidemic effects of apple polyphenols extract(APE)in Triton WR-1339-induced endogenous hyperlipidemic model.Methods:Firstly,APE was isolated and purified from the pomace of Red Fuji Apple and contents of individual polyphenols in APE were determined using highperformance liquid chromatography-mass spectrometry(HPLC-MS).Secondly,forty male National Institude of Health(NIH)mice were randomly divided into 5 groups with 8 animals in each group.The Fenofibrate Capsules(FC)group and APE groups received oral administration of respective drugs for 7 consecutive days.All mice except those in the normal group were intravenously injected through tail vein with Triton WR-1339 on the6th day.Serum and livers from all the mice were obtained 18 h after the injection.The changes in serum total cholesterol(TC),triglyceride(TG),lipoprotein lipase(LPL)and hepatic triglyceride lipase(HTGL)were measured by respective kits.Finally,expression of hepatic peroxisome proliferator-activated receptor alpha(PPARα)mRNA was measured by real-time reverse transcription-polymerase chain reaction(RT-PCR)method.Results:Serum TC and TG levels significantly increased in Triton WR-1339-induced model group compared with the normal group(P<0.01).Oral administration of APE[200 and 400 mg/(kg·day)]dose-dependently reduced the serum level of TG in hyperlipidemic mice(P<0.01).Serum LPL and HTGL activities significantly decreased in Triton WR-1339-induced model group compared with the normal group(P<0.05).Oral administration of APE[200 and 400 mg/(kg·day)]dose-dependently elevated the serum activity of LPL in hyperlipidemic mice(P<0.05or P<0.01).Furthermore,compared with the normal group,hepatic mRNA level of PPARαin the model group significantly decreased(P<0.01).Oral administration of APE[200 and 400 mg/(kg·day)]dose-dependently elevated the expression of PPARαin hyperlipidemic mice(P<0.05 or P<0.01).Conclusion:APE could reduce TG level via up-regulation of LPL activity,which provides new evidence to elucidate the anti-hyperlipidemic effects of APE.
基金Supported by FORICA(the FOundation for Advanced Research in Hypertension and Cardiovascular diseases,www.forica.it)
文摘Atherosclerosis manifests itself clinically at advanced stages when plaques undergo hemorrhage and/or rupture with superimposed thrombosis, thus abruptly stopping blood supply. Identification of markers of plaque destabilization at a pre-clinical stage is, therefore, a major goal of cardiovascular research. Promising results along this line were provided by studies investigating the lipoprotein-associated phospholipase A2(Lp-PLA2), a member of phospholipase A2 proteins family that plays a key role in the metabolism of pro-inflammatory phospholipids, as oxidized low-density lipoproteins, and in the generation of pro-atherogenic metabolites, including lysophosphatidylcholine and oxidized free fatty acids. We herein review the experimental and clinical studies supporting use of Lp-PLA2 activity for predicting cardiovascular events. To his end we considered not only Lp-PLA2 activity and mass, but also Lp-PLA2 gene variations and their association with incident coronary artery disease, stroke, and cardiovascular mortality. Based on these evidences the major scientific societies have included in their guidelines the measurement of Lp-PLA2 activity among the biomarkers that are useful in risk stratification of adult asymptomatic patients at intermediate cardiovascular risk. The results of two recently published major clinical trials with the LpPLA2 inhibitor darapladib, which seem to challenge the pathogenic role of Lp-PLA2, will also be discussed.
文摘Lipoprotein(a) [Lp(a)] is composed of a low density lipoprotein(LDL)-like particle to which apolipoprotein(a)[apo(a)] is linked by a single disulfide bridge. Lp(a) is considered a causal risk factor for ischemic cardiovascular disease(CVD) and calcific aortic valve stenosis(CAVS). The evidence for a causal role of Lp(a) in CVD and CAVS is based on data from large epidemiological databases, mendelian randomization studies, and genome-wide association studies. Despite the well-established role of Lp(a) as a causal risk factor for CVD and CAVS, the underlying mechanisms are not well understood. A key role in the Lp(a) functionality may be played by its oxidized phospholipids(OxPL) content. Importantly, most of circulating OxPL are associated with Lp(a); however, the underlying mechanisms leading to this preferential sequestration of OxPL on Lp(a) over the other lipoproteins,are mostly unknown. Several studies support the hypothesis that the risk of Lp(a) is primarily driven by its OxPL content.An important role in Lp(a) functionality may be played by the lipoprotein-associated phospholipase A_2(Lp-PLA_2),an enzyme that catalyzes the degradation of OxPL and is bound to plasma lipoproteins including Lp(a). The present review article discusses new data on the pathophysiological role of Lp(a) and particularly focuses on the functional role of OxPL and Lp-PLA_2 associated with Lp(a).
文摘Objective: To investigate the mechanism of Astragalus-Angelica Mixture (AAM)’s effects on lipid metabolism disturbance in nephrotic rats.Methods: To examine the effects of AAM on serum albumin, lipid levels, and activities of lipoprotein lipase (LPL) and lecithin-cholesterol acyltransferase (LCAT), which are key enzymes for metabolism of lipid in immune-induced nephrotic hyperlipidemia rats and exogenous hyperlipidemia rats.Results: In nephrotic rats, serum albumin was reduced, lipid increased significantly, LPL activity decreased markedly and the LCAT activity was relatively insufficient. Activities of LPL and LCAT increased obviously in AAM treated nephrotic rats. There were no change of activities of LPL and LCAT in exogenous hyperlipidemia rats and AAM showed no effect on the activities of these two enzymes. Conclusion: The effect of AAM on regulating lipid metabolism might be due to enhance the clearance of both triglyceride-rich and cholesterol-rich apoB containing lipoprotein by improving the activities of LPL and LCAT.
文摘Objective:To evaluate the influence of–250G>A(rs2070895)polymorphism in hepatic lipase gene(LIPC)promoter on plasma lipid parameters of ischemic stroke patients.Methods:A total of 100 stroke patients and 100 control subjects matched for sex(59 men and 41 women)and age were selected.Hepatic lipase activity and lipid profiles were measured while lipoprotein ratios were calculated.Genotyping of the–250G>A promoter polymorphism of the LIPC was performed by the polymerase chain reaction and restriction fragment length polymorphism method combined with 2%gel electrophoresis and then confirmed by direct sequencing.The LIPC promoter gene sequencing data were compared with refseqNG011465.1 LIPC from GenBank.Results:The frequencies of GG,GA and AA genotypes of LIPC rs2070895 polymorphism were 39%,45%and 16%for the control,10%,37%and 53%for the stroke subjects(P<0.0001),respectively.The frequencies of G and A alleles were 61.5%and 38.5%for the control,and 28.5%and 71.5%for the stroke subjects(P<0.0001).Our study shows that the mutant allele of the LIPC promoter was associated with dyslipidemia,lower hepatic lipase activity,and this variation contributed to the increased defective plasma high-density lipoprotein-cholesterol(HDL-C),HDL2-C and HDL3-C concentration for both subjects.The control subjects had 6 single nucleotide polymorphism and 6 amino acid substitutions while the stroke subjects had 32 single nucleotide polymorphism and 20 amino acid substitutions.Conclusions:LIPC–250G>A polymorphism can influence plasma lipid profiles and lipoprotein ratios in patients with ischemic stroke.
文摘Diabetic dyslipidemia is characterized by quantitative and qualitative abnormalities in lipoproteins.In addition to glycation and oxidation,carbamylation is also a post-translational modification affecting lipoproteins in diabetes.Patients with type 2 diabetes(T2D)exhibit higher levels of carbamylated low-density lipoproteins(cLDL)and high-density lipoproteins(cHDL).Accumulating evidence suggests that cLDL plays a role in atherosclerosis in diabetes.cLDL levels have been shown to predict cardiovascular events and all-cause mortality.cLDL facilitates immune cell recruitment in the vascular wall,promotes accumulation of lipids in macrophages,and contributes to endothelial dysf-unction,endothelial nitric oxide-synthase(eNOS)inactivation and endothelial repair defects.Lastly,cLDL induces thrombus formation and platelet aggregation.On the other hand,recent data have demonstrated that cHDL serum level is independently associated with all-cause and cardiovascular-related mortality in T2D patients.This relationship may be causative since the atheroprotective properties of HDL are altered after carbamylation.Thus,cHDL loses the ability to remove cholesterol from macrophages,to inhibit monocyte adhesion and recruitment,to induce eNOS activation and to inhibit apoptosis.Taken together,it seems very likely that the abnormalities in the biological functions of LDL and HDL after carbamylation contribute to atherosclerosis and to the elevated cardiovascular risk in diabetes.
文摘Objective To explore the relationship between the lipoprotein lipase(LPL)-447C/G gene polymorphism and cerebral infarction in the elderly. Methods This was a case-control study,which enrolled 206 cases with cerebral infarction in the elderly and 203
基金financially supported by the National Key Research and Development Program of China (2021YFC2102801)National Natural Science Foundation of China (21878221)+1 种基金the Foundation for Innovative Research Groups of the National Natural Science Foundation of China (21621004)the Haihe Laboratory of Sustainable Chemical Transformations for financial support.
文摘We described a novel polymer-lipase conjugate for high-efficient esterification of vitamin E using vitamin E and succinic anhydride as the substrates in nonaqueous media.In this work,the monomer,N-isopropylacrylamide(NIPAM),was grafted onto Candida rugosa lipase(CRL)to synthesize poly(NIPAM)(pNIPAM)-CRL conjugate by atom transfer radical polymerization via the initiator coupled on the surface of CRL.The result showed that the catalytic efficiencies of pNIPAM-CRL conjugates(19.5-30.3 L·s^(-1)·mmol^(-1))were at least 7 times higher than that of free CRL(2.36 L·s^(-1)·mmol^(-1))in DMSO.It was attributed to a significant increase in Kcat of the conjugates in nonaqueous media.The synthesis catalyzed by pNIPAM-CRL co njugates was influenced by the length and density of the grafted polymer,water content,solvent polarity and molar ratio of the substrates.In the optimal synthesis,the reaction time was shortened at least 7 times,and yields of vitamin E succinate by pNIPAM-g-CRL and free CRL were obtained to be 75.4%and 6.6%at 55℃after the reaction for 1.5 h.The result argued that conjugation with pNIPAM induced conformational change of the lid on CRL based on hydrophobic interaction,thus providing a higher possibility of catalysis-favorable conformation on CRL in nonaqueous media.Moreover,pNIPAM conjugation improved the thermal stability of CRL greatly,and the stability improved further with an increase of chain length of pNIPAM.At the optimal reaction conditions(55℃and 1.5 h),pNIPAM-g-CRL also exhibited good reusability in the enzymatic synthesis of vitamin E succinate and kept~70%of its catalytic activity after ten consecutive cycles.The research demonstrated that pNIPAM-g-CRL was a more competitive biocatalyst in the enzymatic synthesis of vitamin E succinate and exhibited good application potential under harsh industrial conditions.
