Intrarenal renin-angiotensin system (RAS) activation plays a critical role in the development and progression of renal injury. In the kidney, all of the RAS components are present and intrarenal angiotensin II (Ang II...Intrarenal renin-angiotensin system (RAS) activation plays a critical role in the development and progression of renal injury. In the kidney, all of the RAS components are present and intrarenal angiotensin II (Ang II) is formed by multiple independent mechanisms. Angiotensinogen (AGT) is the only known substrate for renin that is a rate-limiting enzyme of the RAS. Recently, enhanced intrarenal AGT levels have been shown to reflect the intrarenal RAS status in hypertension, chronic glomerular disease and diabetic nephropathy. In this review, we focus on AGT expression of the diseased glomeruli in the progression of glomerular disease. An anti-glomerular basement membrane nephritis rat model developed progressive proteinuria and glomerular crescent formation, accompanied by increased macrophage infiltration and glomerular expression of AGT and Ang II. The addition of Ang II type 1 receptor blocker to CC-chemokine recaptor 2 antagonist markedly attenuated the induction of macrophage infiltration, AGT and Ang II, and reduced glomerular crescent formation. Next, the levels of glomerular AGT expression and marker of reactive oxygen species in Zucker diabetic fatty (ZDF) obese rats were higher than those in ZDF lean rats. Hydrogen peroxide (H2O2) induced an increase in the AGT expression in primary rat mesangial cells. Furthermore, the H2O2-induced upregulation of AGT was inhibited by a mitogen-activated protein kinase kinase and a c-Jun N-terminal kinase inhibitor. These data suggest the potential contribution of enhanced AGT expression in glomeruli to the intrarenal RAS activation for the development of glomerular disease.展开更多
AIM To elucidate the profile of the salivary proteome.METHODS Unstimulated whole mouth saliva was collected from 30 volunteers [15 proliferative verrucous leukoplakia(PVL) patients and 15 controls] and proteins were s...AIM To elucidate the profile of the salivary proteome.METHODS Unstimulated whole mouth saliva was collected from 30 volunteers [15 proliferative verrucous leukoplakia(PVL) patients and 15 controls] and proteins were submitted for mass spectrometry-based proteomics using the discovery approach,followed by analyses of variance and logistic regression tests.RESULTS A total of two hundred and eighty-three proteins were confidently identified in saliva.By combining two low abundance proteins from the PVL group,angiotensinogen(AGT) and dipeptidyl peptidase 1(DPP1),a model for group differentiation was built with a concordance index of 94.2%,identifying both proteins as potential etiologic biomarkers for PVL.CONCLUSION This study suggests that both AGT and DPP1 may be involved in developmental mechanisms of PVL.展开更多
The expression and function in growth and apoptosis of the renin-angiotensin system(RAS)was evaluated inhuman glioblastoma.Renin and angiotensinogen(AGT)mRNAs and proteins were found by in situ hybridisationand immuno...The expression and function in growth and apoptosis of the renin-angiotensin system(RAS)was evaluated inhuman glioblastoma.Renin and angiotensinogen(AGT)mRNAs and proteins were found by in situ hybridisationand immunohistochemistry in glioblastoma cells.Angiotensinogen was present in glioblastoma cystic fluids.Thus,human glioblastoma cells produce renin and AGT and secrete AGT.Human glioblastoma and glioblastoma cellsexpressed renin,AGT,renin receptor,AT(2)and/or AT(1)mRNAs and proteins determined by RT-PCR and/展开更多
AIM: To investigated the status of low-density lipoprotein (LDL)-receptor and angiotensionogen gene expression in rats treated chronically with ethanol followed by binge administration, a model that mimics the human s...AIM: To investigated the status of low-density lipoprotein (LDL)-receptor and angiotensionogen gene expression in rats treated chronically with ethanol followed by binge administration, a model that mimics the human scenario. METHODS: Rats were chronically treated with ethanol in liquid diet for 4 wk followed by a single binge mode of ethanol administration (5 mg/kg body weight). Samples were processed 4 h after binge ethanol administration (chronic ethanol binge). Control rats were fed isocaloric diet. In the control for binge, ethanol was replaced by water. Expression of mRNA for angioten-sinogen, c-fos and LDL-receptor, and nuclear accumulation of phospho-extracellular regulated kinases (ERK)1/2 and ERK1/2 protein were examined. RESULTS: Binge ethanol administration in chronically treated rats caused increase in steatosis and necrosis. Chronic ethanol alone had negligible effect on mRNA levels of LDL-receptor, or on the levels of nuclear ERK1/2 and phospho-ERK1/2. But, chronic ethanol followed by binge caused a decrease in LDL-receptor mRNA, and also decreased the levels of ERK1/2 and phospho-ERK1/2 in the nuclear compartment. On the other hand, chronic ethanol-binge increased mRNA expression of angiotensinogen and c-fos. CONCLUSION: Binge ethanol after chronic exposure, causes transcriptional dysregulation of LDL-receptor and angiotensinogen genes, both cardiovascular risk factors.展开更多
Purpose: Local activation of rennin-angiotensin system (RAS) is involved in the progression of chronic kidney disease (CKD). One of the RAS components, angiotensinogen (AGT) has been known to be a potential surrogate ...Purpose: Local activation of rennin-angiotensin system (RAS) is involved in the progression of chronic kidney disease (CKD). One of the RAS components, angiotensinogen (AGT) has been known to be a potential surrogate biomarker for the renal RAS activity. Measuring the daily urinary excretion of AGT (U-AGT), the present study addressed whether the intensive blood pressure (BP) lowering with combined antihypertensive agents could improve such an abnormality in diabetic CKD patients. Methods: Uncontrolled hypertensive patients with type 2 diabetes with mild to moderate nephropathy previously receiving angiotensin receptor blockers (ARB) in an optimal dose alone were recruited for a better blood pressure (BP) control. Urinary specimens were subjected to a quantitative measurement of a daily urinary protein (U-prot) and U-AGT. After the baseline measurement, intensive antihypertensive therapy was attempted by switching the ARB dose to a fixed combination formula of candesartan 8 mg plus hydrochlorthiazide (HCTZ) 6.25 mg and the patients were followed up for 24 weeks. Comparison of parameters was then made between the values at the baseline and the end of the study. Results: At baseline, there was a significant positive correlation between U-AGT and U-prot, and between U-AGT and serum creatinine (Cr) concentration. In addition, U-AGT was inversely correlated with estimated glomerular filtration rate (e-GFR). Switching the antihypertensive regime from ARB alone to the combined ARB/HCTZ significantly reduced BP, U-AGT and U-prot. The magnitude of the reduction in U-prot was positively correlated with that in U-AGT. A stepwise regression analysis showed that HbA1c, e-GFR and the reduction in U-prot in response to the intensive antihypertensive therapy were positively correlated with the reduction in U-AGT. Conclusion: U-AGT is increased and positively correlated with U-prot in patients with type 2 diabetic nephropathy. Intensive antihypertensive treatment with ARB combined with HCTZ reduces both U-AGT and U-prot, presumably via an amelioration of an accelerated renal RAS activity. These data also suggest that U-AGT can be used as a potential therapeutic surrogate biomarker for the activated renal RAS in patients with diabetic nephropathy.展开更多
Objective:To observe the effects of electroacupuncture along meridians on the expression of angiotensinogen(AGT)mRNA in myocardial tissue of myocardial ischemia(MI)rats.Methods:SD rats were randomly divided into four ...Objective:To observe the effects of electroacupuncture along meridians on the expression of angiotensinogen(AGT)mRNA in myocardial tissue of myocardial ischemia(MI)rats.Methods:SD rats were randomly divided into four groups:control group,MI model group,Neiguan(PC6)point group(EA group)and non-acupoint(the lateral-superior side of the hip)group.Myocardial infarction was produced in rats with 85 mg/kg of isoproterenol administered subcutaneously twice at an interval of 24 h.Rats of EA group and non-acupoint group were treated with electroacupuncture,once daily for five consecutive days.Gene chip was used to detect RAS-related genes of myocardial tissue from the model group and the EA group.Cardiac index and pathological staining were observed of four groups.Real-time quantitative fluorescent PCR was used to detect the expression of AGT mRNA in cardiac tissue.Results:The expression of RAS-related genes were different between the model group and the EA group.The difference of AGT mRNA was the most significant.The cardiac index and AGT mRNA expression in the model group were significantly higher than those in the control group(P<0.01).While those in the EA group were significantly lower than model group(P<0.05).The cardiac index and the expressions of AGT mRNA in the nonacupoint group were significantly higher than those in the EA group(P<0.01),and there was no difference with the model group.Conclusion:Electroacupuncture along meridians can improve myocardial ischemia in rats,and its mechanism may be related to the down-regulation of AGT mRNA expression in myocardial tissue.展开更多
OBJECTIVE: To investigate the association between angiotensinogen gene M235T polymorphism and ischemic stroke in East Asians. DATA RETRIEVAL: A computer-based online search was conducted in PubMed, Google scholar, Chi...OBJECTIVE: To investigate the association between angiotensinogen gene M235T polymorphism and ischemic stroke in East Asians. DATA RETRIEVAL: A computer-based online search was conducted in PubMed, Google scholar, China National Knowledge lnfrastructure database between January 1990 and April 2012 for relevant studies. The were angiotensinogen or AGT, polymorphism or genetic and ischemic stroke or cerebral infarction. SELECTION CRITERIA: Case-controlled studies addressing the correlation between angiotensinogen gene M235T polymorphism and ischemic stroke in East Asians were included. The distribution of genotypes in the included studies was tested for Hardy-Weinberg equilibrium. Quality evaluation of the included studies was conducted by two physicians. Statistical analyses were carried out using Stata 12.0 software for meta-analysis. Heterogeneity tests, sensitivity analysis and publication bias were also conducted. MAIN OUTCOME MEASURES: The association between angiotensinogen gene M235T polymorphism and ischemic stroke risk in East Asians was assessed. RESULTS: Six relevant studies involving 891 patients with ischemic stroke and 727 controls were included in this meta-analysis. Results showed that there was a significant association between angiotensinogen gene M235T polymorphism and the risk of ischemic stroke in East Asians (T vs. M: odds ratio (OR) = 1.54, 95% confidence interval (CI) = 1.10-2.16; TT vs. MM: OR = 2.24, 95%CI = 1.37-3.66; TT vs. MT: OR = 1.76, 95%CI = 1.41-2.20; MM + MT vs. TT: OR = 0.57, 95%CI = 0.46-0.70). Sensitivity analysis confirmed that the study results were stable and reliable, with no publication bias. CONCLUSION: The angiotensinogen gene M235T polymorphism is associated with ischemic stroke in East Asians, and the TT genotype and T allele are risk factors for ischemic stroke.展开更多
ObjectiveTo explore the relationship between the mutant genes of ACE,ATN,β 3 AR and hypertension in patients with type 2 DM. Methods281 recruited Chinese subjects were divided into two groups according to the oral gl...ObjectiveTo explore the relationship between the mutant genes of ACE,ATN,β 3 AR and hypertension in patients with type 2 DM. Methods281 recruited Chinese subjects were divided into two groups according to the oral glucose tolerance test (OGTT): ① non diabetes group including normal and impaired glucose tolerance (NGT,IGT): 169 cases;② Type 2 diabetes mellitus (DM): 112 cases. The subjects were genotyped for the ACE gene,the ATN gene and the codon 64 of β 3 AR gene polymorphisms by applying polymerase chain reaction (PCR),PCR restriction fragment length polymorphisms screening with the use of endonuclease. ResultsOur study found that the frequency of D/D genotype and D allele of ACE gene,a/a genotype and an allele of ATN gene in HT patients without DM were increased (P all <0.05);that the frequency of codon 64 mutation of β 3 AR gene also increased in HT patients with NGT (P < 0.05 ). In the model of multiple factors non condition al Logistic regression analyses,HT had relationship with history of hypertension,age and glucose tolerance (OR=10.745 7,1.780 4, 2.034 6;P=0.000 4, 0.000 0 ,0.024 6;respectively),with polymorphism of ATN gene,β 3AR gene,ACE gene (OR= 2.273 6 ,1.935 3,1.830 9;P=0.054 3,0.028 7,0.043 2;resceptively). ConclusionThese results suggest that variants of ACE gene,β 3AR gene,ATN gene were associated with HT in type 2 DM.展开更多
Objective To investigate whether angiotensinogen (AGT) gene M235T variant is associated with non insulin dependent diabetes mellitus without nephropathy (DN -), and diabetic nephropathy (DN +) in Chinese non insulin d...Objective To investigate whether angiotensinogen (AGT) gene M235T variant is associated with non insulin dependent diabetes mellitus without nephropathy (DN -), and diabetic nephropathy (DN +) in Chinese non insulin dependent diabetes mellitus (NIDDM) Methods The subjects in DN + group, DN - group and control group were well matched with sex, age and duration of disease, and the two case groups were divided into two subgroups as with and without hypertension respectively The M235T polymorphism of AGT gene of 84 cases with DN -, 96 patients with DN + and 98 controls were determined by polymerase chain reaction (PCR) amplification and restriction fragment length polymorphism (RFLP) analysis of the region of the variant, i e M235T polymorphism Results The increased frequencies of T allele (0 82) and TT genotype (0 70) were observed in 96 subjects with DN + as compared with 98 control subjects (0 63 and 0 43, respectively, P =0 003, P =0 0004) The odds ratio associated with TT genotype was 3 47 (95%CI: 1 51-7 94; P =0 0033) for diabetic nephropathy in analysis adjusted for several risk factors of diabetic nephropathy, such as body mass index, systolic and diastolic blood pressure, serum cholesterol, low density lipoprotein and high density lipoprotein Subgroup analysis of the 67 patients in DN + group with hypertension revealed similar distributions of M235T genotypes and alleles to those in the DN + without hypertension subgroup There was no difference in allele and genotype distribution between 84 DN - patients and the controls Similarly, frequencies of the AGT M235T genotype and allele were not different between two DN - subgroups Conclusions AGT gene M235T polymorphism is associated with diabetic nephropathy in NIDDM TT genotype of the AGT gene might be an independent risk factor of diabetic nephropathy in Chinese NIDDM展开更多
Objective: To observe the effect of electroacupuncture(EA) stimulation on the expressions of angiotensinogen(AGT), angiotensin Ⅱ type 1 receptor(AT1R), endothelin-1(ET1), and endothelin A receptor(ETAR) m RNA in spon...Objective: To observe the effect of electroacupuncture(EA) stimulation on the expressions of angiotensinogen(AGT), angiotensin Ⅱ type 1 receptor(AT1R), endothelin-1(ET1), and endothelin A receptor(ETAR) m RNA in spontaneously hypertensive rat(SHR) aorta. Methods: Eighteen male SHRs were randomly divided into three groups, an SHR group, an SHR Baihui(DU 20) and Zusanli(ST 36) acupoint(SHR-AP) group, and an SHR non-acupoint(SHR-NAP) group, with 6 rats in each group. Six Wistar rats were used as a control. Rats in the SHR-AP group were stimulated by DU 20 and ST 36 acupoints, both of which were connected with EA. EA was handled one time every Monday, Wednesday and Friday, for total 24 times(8 weeks). SHRNAP rats were acupointed at a 15°angle flat into 0.5 cm to two points, which were 1 and 2 cm from rail tip separately. EA parameters were the same as the SHR-AP rats. SHR control rats and Wistar rats were fixed without EA. Real-time quantitative polymerase chain reaction(PCR) was used to measure AGT, AT1 R, ET1, and ETAR m RNA expression in rat aorta. Results: EA stimulation significantly reduced rat aorta vascular AGT, ET1, ETAR and AT1 R m RNA expressions in the SHR-AP and SHR-NAP groups(P<0.01). Among these four genes, AT1 R m RNA expression was significantly lower in the SHR-AP than in the SHR-NAP group(P<0.01). Conclusion: EA could reduce the AT1 R m RNA expression in SHR-AP rat aorta, indicating a potential mechanism for the hypotensive effects of EA.展开更多
Coronary heart disease (CHD) is a major health problem in many countries and its pathogenesis is not yet fully understood, contributing to significant morbidity and mortality. Accumulated evidence manifest clearly tha...Coronary heart disease (CHD) is a major health problem in many countries and its pathogenesis is not yet fully understood, contributing to significant morbidity and mortality. Accumulated evidence manifest clearly that CHD is determined by a complex interplay of genetic and environmental factors. Many clinical data have showed that the renin-angiotensin system (RAS) involved in many cardiovascular diseases, such as hypertension and CHD. Angiotensinogen (AGT) is the key components of the RAS system, and two gene polymorphisms of AGT had been detected of the CHD risk: M235T and T174M. This article reviews the effects of AGT gene polymorphisms on the CHD.展开更多
文摘Intrarenal renin-angiotensin system (RAS) activation plays a critical role in the development and progression of renal injury. In the kidney, all of the RAS components are present and intrarenal angiotensin II (Ang II) is formed by multiple independent mechanisms. Angiotensinogen (AGT) is the only known substrate for renin that is a rate-limiting enzyme of the RAS. Recently, enhanced intrarenal AGT levels have been shown to reflect the intrarenal RAS status in hypertension, chronic glomerular disease and diabetic nephropathy. In this review, we focus on AGT expression of the diseased glomeruli in the progression of glomerular disease. An anti-glomerular basement membrane nephritis rat model developed progressive proteinuria and glomerular crescent formation, accompanied by increased macrophage infiltration and glomerular expression of AGT and Ang II. The addition of Ang II type 1 receptor blocker to CC-chemokine recaptor 2 antagonist markedly attenuated the induction of macrophage infiltration, AGT and Ang II, and reduced glomerular crescent formation. Next, the levels of glomerular AGT expression and marker of reactive oxygen species in Zucker diabetic fatty (ZDF) obese rats were higher than those in ZDF lean rats. Hydrogen peroxide (H2O2) induced an increase in the AGT expression in primary rat mesangial cells. Furthermore, the H2O2-induced upregulation of AGT was inhibited by a mitogen-activated protein kinase kinase and a c-Jun N-terminal kinase inhibitor. These data suggest the potential contribution of enhanced AGT expression in glomeruli to the intrarenal RAS activation for the development of glomerular disease.
文摘AIM To elucidate the profile of the salivary proteome.METHODS Unstimulated whole mouth saliva was collected from 30 volunteers [15 proliferative verrucous leukoplakia(PVL) patients and 15 controls] and proteins were submitted for mass spectrometry-based proteomics using the discovery approach,followed by analyses of variance and logistic regression tests.RESULTS A total of two hundred and eighty-three proteins were confidently identified in saliva.By combining two low abundance proteins from the PVL group,angiotensinogen(AGT) and dipeptidyl peptidase 1(DPP1),a model for group differentiation was built with a concordance index of 94.2%,identifying both proteins as potential etiologic biomarkers for PVL.CONCLUSION This study suggests that both AGT and DPP1 may be involved in developmental mechanisms of PVL.
文摘The expression and function in growth and apoptosis of the renin-angiotensin system(RAS)was evaluated inhuman glioblastoma.Renin and angiotensinogen(AGT)mRNAs and proteins were found by in situ hybridisationand immunohistochemistry in glioblastoma cells.Angiotensinogen was present in glioblastoma cystic fluids.Thus,human glioblastoma cells produce renin and AGT and secrete AGT.Human glioblastoma and glioblastoma cellsexpressed renin,AGT,renin receptor,AT(2)and/or AT(1)mRNAs and proteins determined by RT-PCR and/
文摘AIM: To investigated the status of low-density lipoprotein (LDL)-receptor and angiotensionogen gene expression in rats treated chronically with ethanol followed by binge administration, a model that mimics the human scenario. METHODS: Rats were chronically treated with ethanol in liquid diet for 4 wk followed by a single binge mode of ethanol administration (5 mg/kg body weight). Samples were processed 4 h after binge ethanol administration (chronic ethanol binge). Control rats were fed isocaloric diet. In the control for binge, ethanol was replaced by water. Expression of mRNA for angioten-sinogen, c-fos and LDL-receptor, and nuclear accumulation of phospho-extracellular regulated kinases (ERK)1/2 and ERK1/2 protein were examined. RESULTS: Binge ethanol administration in chronically treated rats caused increase in steatosis and necrosis. Chronic ethanol alone had negligible effect on mRNA levels of LDL-receptor, or on the levels of nuclear ERK1/2 and phospho-ERK1/2. But, chronic ethanol followed by binge caused a decrease in LDL-receptor mRNA, and also decreased the levels of ERK1/2 and phospho-ERK1/2 in the nuclear compartment. On the other hand, chronic ethanol-binge increased mRNA expression of angiotensinogen and c-fos. CONCLUSION: Binge ethanol after chronic exposure, causes transcriptional dysregulation of LDL-receptor and angiotensinogen genes, both cardiovascular risk factors.
文摘Purpose: Local activation of rennin-angiotensin system (RAS) is involved in the progression of chronic kidney disease (CKD). One of the RAS components, angiotensinogen (AGT) has been known to be a potential surrogate biomarker for the renal RAS activity. Measuring the daily urinary excretion of AGT (U-AGT), the present study addressed whether the intensive blood pressure (BP) lowering with combined antihypertensive agents could improve such an abnormality in diabetic CKD patients. Methods: Uncontrolled hypertensive patients with type 2 diabetes with mild to moderate nephropathy previously receiving angiotensin receptor blockers (ARB) in an optimal dose alone were recruited for a better blood pressure (BP) control. Urinary specimens were subjected to a quantitative measurement of a daily urinary protein (U-prot) and U-AGT. After the baseline measurement, intensive antihypertensive therapy was attempted by switching the ARB dose to a fixed combination formula of candesartan 8 mg plus hydrochlorthiazide (HCTZ) 6.25 mg and the patients were followed up for 24 weeks. Comparison of parameters was then made between the values at the baseline and the end of the study. Results: At baseline, there was a significant positive correlation between U-AGT and U-prot, and between U-AGT and serum creatinine (Cr) concentration. In addition, U-AGT was inversely correlated with estimated glomerular filtration rate (e-GFR). Switching the antihypertensive regime from ARB alone to the combined ARB/HCTZ significantly reduced BP, U-AGT and U-prot. The magnitude of the reduction in U-prot was positively correlated with that in U-AGT. A stepwise regression analysis showed that HbA1c, e-GFR and the reduction in U-prot in response to the intensive antihypertensive therapy were positively correlated with the reduction in U-AGT. Conclusion: U-AGT is increased and positively correlated with U-prot in patients with type 2 diabetic nephropathy. Intensive antihypertensive treatment with ARB combined with HCTZ reduces both U-AGT and U-prot, presumably via an amelioration of an accelerated renal RAS activity. These data also suggest that U-AGT can be used as a potential therapeutic surrogate biomarker for the activated renal RAS in patients with diabetic nephropathy.
基金National Natural Science Foundation of China(No.81804001)Natural Science Foundation of Department of Science and Technology of Fujian Province(No.2018J01858)。
文摘Objective:To observe the effects of electroacupuncture along meridians on the expression of angiotensinogen(AGT)mRNA in myocardial tissue of myocardial ischemia(MI)rats.Methods:SD rats were randomly divided into four groups:control group,MI model group,Neiguan(PC6)point group(EA group)and non-acupoint(the lateral-superior side of the hip)group.Myocardial infarction was produced in rats with 85 mg/kg of isoproterenol administered subcutaneously twice at an interval of 24 h.Rats of EA group and non-acupoint group were treated with electroacupuncture,once daily for five consecutive days.Gene chip was used to detect RAS-related genes of myocardial tissue from the model group and the EA group.Cardiac index and pathological staining were observed of four groups.Real-time quantitative fluorescent PCR was used to detect the expression of AGT mRNA in cardiac tissue.Results:The expression of RAS-related genes were different between the model group and the EA group.The difference of AGT mRNA was the most significant.The cardiac index and AGT mRNA expression in the model group were significantly higher than those in the control group(P<0.01).While those in the EA group were significantly lower than model group(P<0.05).The cardiac index and the expressions of AGT mRNA in the nonacupoint group were significantly higher than those in the EA group(P<0.01),and there was no difference with the model group.Conclusion:Electroacupuncture along meridians can improve myocardial ischemia in rats,and its mechanism may be related to the down-regulation of AGT mRNA expression in myocardial tissue.
基金supported by the Natural Science Foundation of Guangdong Province,No.S2011010005828
文摘OBJECTIVE: To investigate the association between angiotensinogen gene M235T polymorphism and ischemic stroke in East Asians. DATA RETRIEVAL: A computer-based online search was conducted in PubMed, Google scholar, China National Knowledge lnfrastructure database between January 1990 and April 2012 for relevant studies. The were angiotensinogen or AGT, polymorphism or genetic and ischemic stroke or cerebral infarction. SELECTION CRITERIA: Case-controlled studies addressing the correlation between angiotensinogen gene M235T polymorphism and ischemic stroke in East Asians were included. The distribution of genotypes in the included studies was tested for Hardy-Weinberg equilibrium. Quality evaluation of the included studies was conducted by two physicians. Statistical analyses were carried out using Stata 12.0 software for meta-analysis. Heterogeneity tests, sensitivity analysis and publication bias were also conducted. MAIN OUTCOME MEASURES: The association between angiotensinogen gene M235T polymorphism and ischemic stroke risk in East Asians was assessed. RESULTS: Six relevant studies involving 891 patients with ischemic stroke and 727 controls were included in this meta-analysis. Results showed that there was a significant association between angiotensinogen gene M235T polymorphism and the risk of ischemic stroke in East Asians (T vs. M: odds ratio (OR) = 1.54, 95% confidence interval (CI) = 1.10-2.16; TT vs. MM: OR = 2.24, 95%CI = 1.37-3.66; TT vs. MT: OR = 1.76, 95%CI = 1.41-2.20; MM + MT vs. TT: OR = 0.57, 95%CI = 0.46-0.70). Sensitivity analysis confirmed that the study results were stable and reliable, with no publication bias. CONCLUSION: The angiotensinogen gene M235T polymorphism is associated with ischemic stroke in East Asians, and the TT genotype and T allele are risk factors for ischemic stroke.
文摘ObjectiveTo explore the relationship between the mutant genes of ACE,ATN,β 3 AR and hypertension in patients with type 2 DM. Methods281 recruited Chinese subjects were divided into two groups according to the oral glucose tolerance test (OGTT): ① non diabetes group including normal and impaired glucose tolerance (NGT,IGT): 169 cases;② Type 2 diabetes mellitus (DM): 112 cases. The subjects were genotyped for the ACE gene,the ATN gene and the codon 64 of β 3 AR gene polymorphisms by applying polymerase chain reaction (PCR),PCR restriction fragment length polymorphisms screening with the use of endonuclease. ResultsOur study found that the frequency of D/D genotype and D allele of ACE gene,a/a genotype and an allele of ATN gene in HT patients without DM were increased (P all <0.05);that the frequency of codon 64 mutation of β 3 AR gene also increased in HT patients with NGT (P < 0.05 ). In the model of multiple factors non condition al Logistic regression analyses,HT had relationship with history of hypertension,age and glucose tolerance (OR=10.745 7,1.780 4, 2.034 6;P=0.000 4, 0.000 0 ,0.024 6;respectively),with polymorphism of ATN gene,β 3AR gene,ACE gene (OR= 2.273 6 ,1.935 3,1.830 9;P=0.054 3,0.028 7,0.043 2;resceptively). ConclusionThese results suggest that variants of ACE gene,β 3AR gene,ATN gene were associated with HT in type 2 DM.
文摘Objective To investigate whether angiotensinogen (AGT) gene M235T variant is associated with non insulin dependent diabetes mellitus without nephropathy (DN -), and diabetic nephropathy (DN +) in Chinese non insulin dependent diabetes mellitus (NIDDM) Methods The subjects in DN + group, DN - group and control group were well matched with sex, age and duration of disease, and the two case groups were divided into two subgroups as with and without hypertension respectively The M235T polymorphism of AGT gene of 84 cases with DN -, 96 patients with DN + and 98 controls were determined by polymerase chain reaction (PCR) amplification and restriction fragment length polymorphism (RFLP) analysis of the region of the variant, i e M235T polymorphism Results The increased frequencies of T allele (0 82) and TT genotype (0 70) were observed in 96 subjects with DN + as compared with 98 control subjects (0 63 and 0 43, respectively, P =0 003, P =0 0004) The odds ratio associated with TT genotype was 3 47 (95%CI: 1 51-7 94; P =0 0033) for diabetic nephropathy in analysis adjusted for several risk factors of diabetic nephropathy, such as body mass index, systolic and diastolic blood pressure, serum cholesterol, low density lipoprotein and high density lipoprotein Subgroup analysis of the 67 patients in DN + group with hypertension revealed similar distributions of M235T genotypes and alleles to those in the DN + without hypertension subgroup There was no difference in allele and genotype distribution between 84 DN - patients and the controls Similarly, frequencies of the AGT M235T genotype and allele were not different between two DN - subgroups Conclusions AGT gene M235T polymorphism is associated with diabetic nephropathy in NIDDM TT genotype of the AGT gene might be an independent risk factor of diabetic nephropathy in Chinese NIDDM
文摘Objective: To observe the effect of electroacupuncture(EA) stimulation on the expressions of angiotensinogen(AGT), angiotensin Ⅱ type 1 receptor(AT1R), endothelin-1(ET1), and endothelin A receptor(ETAR) m RNA in spontaneously hypertensive rat(SHR) aorta. Methods: Eighteen male SHRs were randomly divided into three groups, an SHR group, an SHR Baihui(DU 20) and Zusanli(ST 36) acupoint(SHR-AP) group, and an SHR non-acupoint(SHR-NAP) group, with 6 rats in each group. Six Wistar rats were used as a control. Rats in the SHR-AP group were stimulated by DU 20 and ST 36 acupoints, both of which were connected with EA. EA was handled one time every Monday, Wednesday and Friday, for total 24 times(8 weeks). SHRNAP rats were acupointed at a 15°angle flat into 0.5 cm to two points, which were 1 and 2 cm from rail tip separately. EA parameters were the same as the SHR-AP rats. SHR control rats and Wistar rats were fixed without EA. Real-time quantitative polymerase chain reaction(PCR) was used to measure AGT, AT1 R, ET1, and ETAR m RNA expression in rat aorta. Results: EA stimulation significantly reduced rat aorta vascular AGT, ET1, ETAR and AT1 R m RNA expressions in the SHR-AP and SHR-NAP groups(P<0.01). Among these four genes, AT1 R m RNA expression was significantly lower in the SHR-AP than in the SHR-NAP group(P<0.01). Conclusion: EA could reduce the AT1 R m RNA expression in SHR-AP rat aorta, indicating a potential mechanism for the hypotensive effects of EA.
文摘Coronary heart disease (CHD) is a major health problem in many countries and its pathogenesis is not yet fully understood, contributing to significant morbidity and mortality. Accumulated evidence manifest clearly that CHD is determined by a complex interplay of genetic and environmental factors. Many clinical data have showed that the renin-angiotensin system (RAS) involved in many cardiovascular diseases, such as hypertension and CHD. Angiotensinogen (AGT) is the key components of the RAS system, and two gene polymorphisms of AGT had been detected of the CHD risk: M235T and T174M. This article reviews the effects of AGT gene polymorphisms on the CHD.
