von Willebrand factor A(vWA)genes are well characterized in humans except for few BONZAI genes,but the vWA genes are least explored in plants.Considering the novelty and vital role of vWA genes,this study aimed at cha...von Willebrand factor A(vWA)genes are well characterized in humans except for few BONZAI genes,but the vWA genes are least explored in plants.Considering the novelty and vital role of vWA genes,this study aimed at characterization of vWA superfamily in rice.Rice genome was found to have 40 vWA genes distributed across all the 12 chromosomes,and 20 of the 40 vWA genes were unique while the remaining shared large fragment similarities with each other,indicating gene duplication.In addition to vWA domain,vWA proteins possess other different motifs or domains,such as ubiquitin interacting motif in protein degradation pathway,and RING finger in protein-protein interaction.Expression analysis of vWA genes in available expression data suggested that they probably function in biotic and abiotic stress responses including hormonal response and signaling.The frequency of transposon elements in the entire 3K rice germplasm was negligible except for 9 vWA genes,indicating the importance of these genes in rice.Structural and functional diversities showed that the vWA genes in a blast-resistant rice variety Tetep had huge variations compared to blast-susceptible rice varieties HP2216 and Nipponbare.qRT-PCR analysis of vWA genes in Magnaporthe oryzae infected rice tissues indicated OsvWA9,OsvWA36,OsvWA37 and OsvWA18 as the optimal candidate genes for disease resistance.This is the first attempt to characterize vWA gene family in plant species.展开更多
BACKGROUND The elevation of plasma von Willebrand factor(vWF)has been proposed to be a predictor of lung cancer.Type 2 diabetes mellitus(T2DM)causes endothelial activation,resulting in the secretion of vWF.However,the...BACKGROUND The elevation of plasma von Willebrand factor(vWF)has been proposed to be a predictor of lung cancer.Type 2 diabetes mellitus(T2DM)causes endothelial activation,resulting in the secretion of vWF.However,the role of vWF in patients with T2DM complicated with lung cancer remains unclear.AIM To investigate the clinical value of serum vWF as a tumor marker in patients with T2DM combined with lung adenocarcinoma in situ(AIS).METHODS This study enrolled 43 patients with T2DM combined with lung AIS(T2DM+AIS group),43 patients with T2DM alone(T2DM group),43 patients with lung AIS alone(AIS group),and 43 healthy volunteers(control group).The serum levels of vWF,insulin-like growth factor 1,and insulin-like growth factor binding protein 3 were determined.Multiple linear stepwise regression was performed to determine the correlations among variables.RESULTS Serum concentration of vWF in the T2DM+AIS group was significantly higher than those in the T2DM,AIS,and control groups(P<0.05).Serum vWF levels in the T2DM and AIS groups were significantly higher than that in the control group(P<0.05).There was no significant difference in serum vWF level between the T2DM and AIS groups.In the T2DM+AIS group,serum vWF was independently associated and positively correlated with serum levels of insulinlike growth factor 1 and insulin-like growth factor binding protein 3(P<0.05).CONCLUSION Serum vWF level may represent a novel biomarker for the early diagnosis of lung AIS.展开更多
AIM: To evaluate the correlations of plasma von Willebrand factor (vWF) level with the distant metastasis and prognosis of patients with colorectal cancer. METHODS: A total of 86 patients with histologically confirmed...AIM: To evaluate the correlations of plasma von Willebrand factor (vWF) level with the distant metastasis and prognosis of patients with colorectal cancer. METHODS: A total of 86 patients with histologically confirmed metastatic colorectal cancers receiving treatment at Taipei Veterans General Hospital were enrolled. All patients had measurable metastatic lesions and life expectancies of more than 3 mo. Plasma vWF levels were measured by immuno-turbidimetric assay and compared with results from 40 non-metastatic colorectal cancer patients and 22 healthy controls. Patients with metastatic colorectal cancer were divided into two groups according to serum vWF levels and the differences between these two groups were analyzed using x2 test. Data on age, gender, performance status, location of primary tumor, extent of metastasis, site of metastases, histological differentiation, serum CEA and plasma vWF levels were analyzed to determine association with survival. Survival curves were constructed by Kaplan-Meier product limit method and the data was analyzed using log-rank test on a microcomputer. Multivariate analysis using the Cox's proportional hazards regression model was then performed to determine the independent prognostic indicators among all of the possible variables.RESULTS: Colorectal cancer patients were identified as having significantly higher plasma vWF concentrations than healthy controls (P＜0.05). Moreover, higher vWF plasmalevels were associated with advanced tumor stage (P＜0.05) and the presence of multiple metastases (P = 0.014).Patients with lower vWF plasma levels (≤ 160%) survived significantly longer than those with a higher plasma vWF level (log-rank test, P = 0.0043). By multivariate analysis,plasma vWF levels (P＜0.001), the extent of metastasis (P = 0.012), and the performance status (P = 0.014)were identified as independent prognostic factors. CONCLUSION: Our data indicates that high plasma vWF concentrations correlate with advanced diseases and significantly poor prognosis of patients with metastatic colorectal carcinoma. It may serve as a potential biological marker of disease progression in these patients.展开更多
AIM: To investigate the levels of D-dimer(DD) and vonWillebrand factor(vWF) and the relationship between DDand vWF in ulcerative colitis(UC) patients.METHODS: A total of 29 plasma specimens were obtainedfrom patients ...AIM: To investigate the levels of D-dimer(DD) and vonWillebrand factor(vWF) and the relationship between DDand vWF in ulcerative colitis(UC) patients.METHODS: A total of 29 plasma specimens were obtainedfrom patients with ulcerative colitis (male 13, female 16),aged 21-47 years (33 + 11). Disease activity was assessed byTruelove-Writeria. Patients with a score of above 5 wereregarded as having active colitis. Twenty healthy people(male 12, female 8),aged 19-53 years(31 + 14), ssrved asnormal controls. Blood samples were taken from anantecubital vein puncture. Blood(1.8 mL) was injected intothe tubes containing sodium citrate (0. 13 mmol/L). Theplasma was obtained by centrifugation at 3000 r@ min-1 for 10min, and stored at -80 ℃ until assayed by ELISA.RESULTS: The mean plasma levels of DD and vWF in activeUC patients were significantly higher than those of thecontrols(0.69+0.41 vs0.27+0.11, P＜0.01;143+46 vs103 + 35, P ＜ 0.01 ). The mean plasma levels of DD in thepatients with active disease were higher than those withinactive disease(0. 69 + 0. 41 vs 0.48+0.29, P＜0.05). Thelevls of v WF were not different between active and inactivepatients. DD levels were positively related to vWF levels( r =0.574, P ＜ 0. 01 ). There was no significant differencebetween levels of DD and vWF and the scope of disease cndsex of the patients.CONCLUSION: vWF is an important feature and a goodmarker of UC; intravascular thrombus and endothelial celldysfunction were found in UC patients; and the combinedtest of DD and vWF is helpful to distinguish the activity ofthe UC patients.展开更多
The present study examined von Willebrand factor (vWF) levels and ADAMTS13 activity in pregnant and severe preeclamptic women in order to shed light on the prothrombotic state in severe preeclampsia.Thirty healthy wom...The present study examined von Willebrand factor (vWF) levels and ADAMTS13 activity in pregnant and severe preeclamptic women in order to shed light on the prothrombotic state in severe preeclampsia.Thirty healthy women of childbearing age,22 second trimester pregnant women,30 third trimester pregnant women and 10 severe preeclamptic patients were recruited in this study.ADAMTS13 activity was determined by the FRETS-vWF73 assay and vWF antigen (vWF:Ag) levels by an enzyme-linked immunosorbent assay.The results showed that there were statistically significant differences in plasma vWF antigen levels between the severe preeclamptic and third trimester pregnant women,between third and second trimester pregnant women (P<0.05).The third trimester pregnant women had significantly lower plasma ADAMTS13 activity than second trimester pregnant women (P<0.05).Nevertheless,no significant differences in plasma ADAMTS13 activity were found between severe preeclamptic patients and the third trimester pregnant women (P>0.05).In conclusion,plasma ADAMTS13 activity is normal in severe preeclampsia despite the increased vWF:Ag levels.Prothrombotic state is involved in the pathogenesis of severe preeclampsia,as a result of endothelial injury.展开更多
AIM To evaluate the levels of von Willebrand factor(VWF) and metalloproteinase with thrombospondin type-1 motif, number 13(ADAMTS13) in inflammatory bowel disease(IBD) and correlate them with the disease activity.METH...AIM To evaluate the levels of von Willebrand factor(VWF) and metalloproteinase with thrombospondin type-1 motif, number 13(ADAMTS13) in inflammatory bowel disease(IBD) and correlate them with the disease activity.METHODS Consecutive patients with IBD aged 18 years or older were enrolled in the study. Forty-seven patients with ulcerative colitis(UC), 38 with Crohn's disease(CD), and 50 healthy controls were included. The white blood cell count, haematocrit, platelet count, fibrinogen, partial activated thromboplastin time, C-reactive protein, albumin, VWF antigen level(VWF:Ag), VWF ristocetin cofactor activity(VWF:RCo), VWF collagen-binding activity(VWF:CB), and ADAMTS13 antigen level(ADAMTS13:Ag) and activity(ADAMTS13act) were measured. The following ratios were assessed: V W F : R C o/V W F : A g, V W F : C B/V W F : A g, V W F : A g/ADAMTS13 act, and ADAMTS13act/ADAMTS13:Ag. RESULTS Compared to controls, the odds ratio(OR) of an elevated VWF: Ag > 150% was 8.7(95%CI: 2.7-28.1) in the UC group and 16.2(95%CI: 4.8-54.0) in the CD group. VWF:CB was lower in UC patients, and active CD was associated with a higher VWF: RCo(+38%). The ORs of VWF:CB/VWF:Ag < 0.7(a marker of acquired von Willebrand syndrome) in the UC and CD groups were 11.9(95%CI: 4.4-32.4) and 13.3(95%CI: 4.6-38.1), respectively. Active UC was associated with lower ADAMTS13:Ag(-23%) and ADAMTS13act(-20%) compared to UC in remission. Patients with active CD had a 15% lower ADAMTS13 act than controls. The activity of UC, but not that of CD, was inversely correlated with ADAMTS13:Ag(r =-0.76) and ADAMTS13act(r =-0.81). CONCLUSION Complex VWF-ADAMTS13-mediated mechanisms disturb haemostasis in IBD. A reduced WVF:CB is a risk factor for bleeding, while a lower ADAMTS13 level combined with an elevated VWF:Ag could predispose one to thrombosis.展开更多
AIM: To evaluate the plasma von Willebrand factor (vWF) levels in patients with ulcerative colitis (UC) and to investigate their relationship with disease activity,systemic inflammation and coagulation activation.METH...AIM: To evaluate the plasma von Willebrand factor (vWF) levels in patients with ulcerative colitis (UC) and to investigate their relationship with disease activity,systemic inflammation and coagulation activation.METHODS: In 46 patients with ulcerative colitis (active in 34 patients), clinical data were gathered and plasma vWF levels, markers of inflammation (ESR, CRP, and fibrinogen) and thrombin generation (TAT, F1+2, and D-dimers) were measured at baseline and after 12 wk of treatment. Plasma vWF levels were also determined in 52 healthy controls (HC). The relationship of plasma vWF levels with disease activity, disease extent, response to therapy, acute-phase reactants (APRs) and coagulation markers (COAGs) was assessed.RESULTS: The mean plasma vWF concentrations were significantly higher in active UC patients (143.38±63.73%) than in HC (100.75±29.65%, P = 0.001)and inactive UC patients (98.92±43.6%, P = 0.031).ESR, CRP and fibrinogen mean levels were significantly higher in active UC patients than in inactive UC patients,whereas there were no significant differences in plasma levels of D-dimers, F1+2, and TAT. UC patients with raised APRs had significantly higher mean plasma vWF levels than those with normal APRs (144.3% vs 96.2%,P = 0.019), regardless of disease activity. Although the mean plasma vWF levels were higher in UC patients with raised COAGs than in those with normal COAGs,irrespective of disease activity, the difference was not significant (141.3% vs 118.2%, P = 0.216). No correlation was noted between plasma vWF levels and disease extent. After 12 wk of treatment, significant decreases of fibrinogen, ESR, F1+2, D-dimers and vWF levels were noted only in UC patients with clinical and endoscopic improvement.CONCLUSION: Our data indicate that increased plasma vWF levels correlate with active ulcerative colitis and increased acute-phase proteins. Elevated plasma vWF levels in ulcerative colitis possibly reflect an acutephase response of the perturbed endothelium due to inflammation. In UC patients, plasma vWF levels may be another useful marker of disease activity or response to therapy.展开更多
Increased thrombotic potential within the liver sinusoids due to local endothelial production of von Willebrand factor antigen macromolecules could represent an additional therapeutic target of portal hypertension in ...Increased thrombotic potential within the liver sinusoids due to local endothelial production of von Willebrand factor antigen macromolecules could represent an additional therapeutic target of portal hypertension in patients with cirrhosis. In this case, anti-inflammatory and antithrombotic drugs could modulate portal pressure by preventing the formation of intrahepatic platelet-induced microthrombi.展开更多
BACKGROUND Many advanced hepatocellular carcinoma(HCC) patients are receiving sorafenib treatment. Sorafenib reportedly improves overall survival(OS) significantly in patients with HCC. Prediction of sorafenib respons...BACKGROUND Many advanced hepatocellular carcinoma(HCC) patients are receiving sorafenib treatment. Sorafenib reportedly improves overall survival(OS) significantly in patients with HCC. Prediction of sorafenib response and prognosis in patients with HCC receiving sorafenib treatment are important due to the potentially serious side effects of sorafenib. A disintegrin-like and metalloproteinase with thrombospondin type-1 motifs 13(ADAMTS13) and von Willebrand factor(VWF) are associated with the pathophysiology of liver cirrhosis and HCC through their roles in hypercoagulability; they are also associated with angiogenesis via vascular endothelial growth factor(VEGF). The imbalance between ADAMTS13 and VWF was associated with prognosis of various cancers in patients undergoing chemotherapy.AIM To investigate ADAMTS13 and VWF as potential biomarkers for sorafenib response and prognosis in patients with HCC receiving sorafenib treatment.METHODS Forty-one patients with HCC receiving sorafenib treatment were included in this study. The initial daily sorafenib dose was 400 mg in all patients. ADAMTS13 activity(ADAMTS13:AC), VWF antigen(VWF:Ag), VEGF levels were determined by enzyme-linked immunosorbent assay. Univariate andmultivariate analyses were used to determine predictive factors for sorafenib response and prognosis in patients with HCC receiving sorafenib treatment.RESULTS ADAMTS13:AC was significantly higher in patients with stable disease(SD),partial response(PR), and complete response(CR) than in those with progressive disease(PD)(P < 0.05). In contrast, VWF:Ag and the VWF:Ag/ADAMTS13:AC ratio were significantly lower in patients with SD, PR, and CR than in those with PD(P < 0.05 for both). Multivariate analysis showed that the VWF:Ag/ADAMTS13:AC ratio was the only predictive factor for sorafenib response and ADAMTS13:AC was the only prognostic factor in patients with HCC receiving sorafenib treatment. The patients with a low ADAMTS13:AC(<78.0) had significantly higher VEGF levels than those with a high ADAMTS13:AC(≥ 78.0)(P < 0.05).CONCLUSION The VWF:Ag/ADAMTS13:AC ratio and ADAMTS13:AC are potentially useful biomarkers for sorafenib response and prognosis, respectively, in patients with HCC receiving sorafenib treatment.展开更多
TO THE EDITOR
Cancer patients usually present a prothrombotic condition.Several clotting-related proteins, such as yon Willebrand factor (vWF), presenting higher plasma concentrations in these patients, may play a key...TO THE EDITOR
Cancer patients usually present a prothrombotic condition.Several clotting-related proteins, such as yon Willebrand factor (vWF), presenting higher plasma concentrations in these patients, may play a key role in this process. Moreover,some of those proteins are currently being characterized as response rate and overall survival markers in metastatic colorectal cancer (MCRC). In this comment article, we discuss the last piece of evidence that supports the use of vWF as a prognostic indicator in MCRC patients, provided by a paper recently published by Wang et al., in the World Journal of Gastroenterology. Summarizing, although vWF should be seriously considered as potential future prognostic and predictive indicator in colorectal cancer, more dynamic and better designed studies in longer series of patients should be conducted before standardizing its universal use among these patients.展开更多
Objective: To explore the role of cytokines on the pathogenesis of atherosclerosis, and the lectins (Ps), von Willebrand (vWF), and D-dimer (D-D) in atherosclerosis (AS) patients. Methods: Sixtythree AS patients were ...Objective: To explore the role of cytokines on the pathogenesis of atherosclerosis, and the lectins (Ps), von Willebrand (vWF), and D-dimer (D-D) in atherosclerosis (AS) patients. Methods: Sixtythree AS patients were randomly divided into the treated group ( n = 33, treated with TMJZ, 10 ml each time, three times a day) and the control group (n = 30, treated with Lovastatin, 10 mg, once daily). The levels of serum lipids (enzymatic methods), Ps, vWF, and D-D were measured before and after 8 weeks of treatment. Results: Serum total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), apo-protein B-100 (apoB-100) were significantly decreased (P＜0.05 or P＜ 0.01) and high-density lipoprotein cholesterol (HDL-C) was significantly raised (P＜0.05) after TM JZ treatment. Serum Ps,vWF, and D-D also declined (P＜0.05) after treatment. There was no significant difference between the treated and the control groups in these parameters except serum HDL-C level. Conclusion: TMJZ has good therapeutic effect in regulating serum lipids, improving endothelial cell function, inhibiting activation of platelets, and preventing the disturbance of blood coagulation/fibrinolysis function in patients with AS.展开更多
Recently the article“Perioperative von Willebrand factor dynamics are associated with liver regeneration and predict outcome after liver resection”was published in Hepatology[1].Prof.Starlinger et al.aimed to assess...Recently the article“Perioperative von Willebrand factor dynamics are associated with liver regeneration and predict outcome after liver resection”was published in Hepatology[1].Prof.Starlinger et al.aimed to assess the association of von Willebrand factor(vWF)levels and clinical outcome in patients with liver cancers post-liver resection(LR).展开更多
Background: Bleeding esophageal varices (OVs) due to portal hypertension are one of the major complications with high mortality in liver cirrhosis. So, early detection and management are mandatory. Aim: To evaluate th...Background: Bleeding esophageal varices (OVs) due to portal hypertension are one of the major complications with high mortality in liver cirrhosis. So, early detection and management are mandatory. Aim: To evaluate the role of Von Willebrand factor (VWF) in predicting the presence of OVs. Patients and Methods: 62 patients with liver cirrhosis representing different Child-Pugh classes were included. The diagnosis of liver cirrhosis was based on the combination of clinical, laboratory and US examinations. All included patients underwent the following investigations: complete blood count, liver function tests (ALT, AST, serum bilirubin, albumin and total protein, prothrombin time (PT) and concentration (PC), INR and serum alkaline phosphatase), serum creatinine, Von Willebrand factor antigen (VWF-Ag) measurement and abdominal US. Upper endoscopic evaluation was done to detect presence or absence of varices (esophageal or gastric) and/or PHG. Results: 38 males and 24 females with their mean age (46 ± 12 years old) were included. Plasma Von Willebrand factor-Ag level was significantly higher in patients with OVs than those without varices (P value = 0.000). Also, its level was significantly higher in patients with higher grade of OVs, G3 than those with G1 or G2 (P value = 0.000). Patients with large OVs including those with G2 and G3 showed significantly higher values of VWF than those with small OVs (NO and G1) (P value = 0.000). VWF was independent predictor for detecting the presence of OVs with good sensitivity (90), specificity (77.3) and accuracy (85.5) at a cutoff value of 1.74 U/ml. Also it was an independent predictor for detecting the presence of large OVs with good sensitivity (91.2), specificity (85.7) and accuracy (88.7) at a cutoff value of 2.16 U/ml. Conclusion: VWF-Ag could be used as a non invasive laboratory independent predictor for the detection of OVs.展开更多
von Willebrand factor (vWF) is an important compound in the human plasma. which is synthesized by endotlrelial cells and also by megakaryocytes. The gene for vWF is located near the tip of the short arm of chromosome ...von Willebrand factor (vWF) is an important compound in the human plasma. which is synthesized by endotlrelial cells and also by megakaryocytes. The gene for vWF is located near the tip of the short arm of chromosome 12, being approximately 180 kb in length and consisting of 52 exons separated by 51 introns. The mature vWF subunit consists of 2 050 amino acid residues with molecular weight of about 250 ku. In plasma vWF appears as various multimers. vWF has two well-characterized functions.展开更多
Von Willebrand Factor(VWF)is a concatameric glycoprotein that plays a key role in rapid hemostasis and thrombosis.VWF has different functional domains that can bind to various molecules such as collagen,hemostatic fac...Von Willebrand Factor(VWF)is a concatameric glycoprotein that plays a key role in rapid hemostasis and thrombosis.VWF has different functional domains that can bind to various molecules such as collagen,hemostatic factorⅧ,integrin,and platelet glycoprotein lbα(GPlbα)to achieve multiple biological functions.During hemostasis,the A1 domain of VWF binds to GPIbαwhere platelets accumulate in the injured vascular endothelium.Due to forces generated by the hemodynamic gradient flow,the relations of bond-dissociation rates versus forces show that the lifetime of molecular bond has multiple states under the external force.We processed the experimental data of receptor-ligand in a single molecule obtained from optical tweezers by two different methods,including a Dudko-Hummer-Szabo equation,and another method combining force4ime history and force induced bond rupture.Then we used a recently developed physical equation regarding protein unfolding rate to fit our results.The lifetime of the bond between A1 and GPlbαobtained by the above mentioned two methods shows a'three-stage'change upon gradually increasing the external force.When the external force was below 8 pN,the lifetime of the bond deceased as the external force increased,which is a typical expression of a catch bond.The lifetime of the bond started to increase when the external force increased from 8 to 11 pN,and then decrease again when the external force increased to above 11 pN.Kim et al.used different processing methods and proposes a'flex-bond'model:the lifetime of the bond will decrease as the external force increases,then suddenly increase to a peak,and continue to decrease with the increase of force.A recently developed model based on the structural-elastic properties of molecules fits our data well,indicating that the bond formed by Al and GPlbαhas a catch-bond phenomenon in a certain interval of external forces,and a flex bond in other force intervals.In conclusion,A1-GPIbαbond will have a'slip-catch-slip'bond tendency.Our result provides a alternative understanding about the role of Al-GPlbαinteractions in the mechanism of hemostasis.展开更多
Objectives: Bleeding from gastroesophageal varices is the most serious and life-threatening complication of cirrhosis and accounts for 10% of all cases of bleeding from the upper GI tract. It is essential to identify ...Objectives: Bleeding from gastroesophageal varices is the most serious and life-threatening complication of cirrhosis and accounts for 10% of all cases of bleeding from the upper GI tract. It is essential to identify and treat those patients at the highest risk because each episode of variceal hemorrhage carries a 20 percent to 30 percent risk of death, and up to 70 percent of patients who do not receive treatment die within one year of the initial bleeding episode. The aim of this study is to determine the clinical predictors of bleeding esophageal varices and study the role of F VII (factor VII) and vWF (von willebrand factor) in predicting bleeding in patients with eosphogeal varices. Methods: A case control study was done on all patients with esophageal varices admitted at Sohag and Qena faculty of medicine hospitals from January 2012 to August 2013. Various clinical, laboratory and endoscopic variables were tested to determine the predictors of esophageal bleeding. Results: Among 300 patients with esophageal varices, 80 percent was due to hepatitis C virus (HCV), 18 percent was due to hepatitis B virus (HBV), and 2 percent had both HCV and HBV. As an etiologic factor for their liver disease, hemoglobin was 10.12 ± 2.26 g/l, platelet count 135.55 ± 65.94 × l09/l, prothrombin time 14.1 ± 0.92 second, albumin 2.88 ± 0.71 g/dl, ALT 48.25 ± 24.15 u/l, total bilirubin 1.92 ± 1.36 mg/dl. Factor VII was 27.4 ± 8.92 percent and vWF was 188.33 ± 13.66 IU/dl. Splenomegaly was reported 79.6 percent, 90.3 percent had ascites. 35 percent had grade III esophageal varices, 29 percent had four-column esophageal varices on endoscopy, 13.7 percent had concomitant gastric varices and 38.3 percent had portal hypertensive gastropathy. Platelet count, presence of red color sign, the number of columns of esophageal varices, presence of portal gastropathy on eosphagogastroduodenoscopy (EGD) showed a significant positive correlation with bleeding. There is a significant decrease of FVII and a significant increase of vWF in bleeding group in comparison with non bleeding group. Conclusion: Thrombocytopenia, presence of encephalopathy and endoscopic findings of large varices, presence of red color sign, and portal hypertensive gastropathy were found to be predictors of esophageal variceal bleeding. Increase of vWF and decrease of FVII are laboratory predictors of esophageal variceal bleeding.展开更多
Traumatic brain injury(TBI)-induced coagulopathy has increasingly been recognized as a significant risk factor for poor outcomes,but the pathogenesis remains poorly understood.In this study,we aimed to investigate the...Traumatic brain injury(TBI)-induced coagulopathy has increasingly been recognized as a significant risk factor for poor outcomes,but the pathogenesis remains poorly understood.In this study,we aimed to investigate the causal role of acrolein,a typical lipid peroxidation product,in TBI-induced coagulopathy,and further explore the underlying molecular mechanisms.We found that the level of plasma acrolein in TBI patients suffering from coagulopathy was higher than that in those without coagulopathy.Using a controlled cortical impact mouse model,we demonstrated that the acrolein scavenger phenelzine prevented TBI-induced coagulopathy and recombinant ADAMTS-13 prevented acrolein-induced coagulopathy by cleaving von Willebrand factor(VWF).Our results showed that acrolein may contribute to an early hypercoagulable state after TBI by regulating VWF secretion.mRNA sequencing(mRNA-seq)and transcriptome analysis indicated that acrolein over-activated autophagy,and subsequent experiments revealed that acrolein activated autophagy partly by regulating the Akt/mTOR pathway.In addition,we demonstrated that acrolein was produced in the perilesional cortex,affected endothelial cell integrity,and disrupted the blood-brain barrier.In conclusion,in this study we uncovered a novel pro-coagulant effect of acrolein that may contribute to TBI-induced coagulopathy and vascular leakage,providing an alternative therapeutic target.展开更多
基金the Indian Council of Agricultural Research(ICAR)-National Institute for Plant Biotechnology,National Agricultural Higher Education Project:Centre for Advanced Agricultural Science and Technology(Grant No.1010033)ICAR-Centre for Agricultural Bioinformatics,Indian Agricultural Statistics Research Institute,New Delhi(IASRI)(Grant No.1006456).
文摘von Willebrand factor A(vWA)genes are well characterized in humans except for few BONZAI genes,but the vWA genes are least explored in plants.Considering the novelty and vital role of vWA genes,this study aimed at characterization of vWA superfamily in rice.Rice genome was found to have 40 vWA genes distributed across all the 12 chromosomes,and 20 of the 40 vWA genes were unique while the remaining shared large fragment similarities with each other,indicating gene duplication.In addition to vWA domain,vWA proteins possess other different motifs or domains,such as ubiquitin interacting motif in protein degradation pathway,and RING finger in protein-protein interaction.Expression analysis of vWA genes in available expression data suggested that they probably function in biotic and abiotic stress responses including hormonal response and signaling.The frequency of transposon elements in the entire 3K rice germplasm was negligible except for 9 vWA genes,indicating the importance of these genes in rice.Structural and functional diversities showed that the vWA genes in a blast-resistant rice variety Tetep had huge variations compared to blast-susceptible rice varieties HP2216 and Nipponbare.qRT-PCR analysis of vWA genes in Magnaporthe oryzae infected rice tissues indicated OsvWA9,OsvWA36,OsvWA37 and OsvWA18 as the optimal candidate genes for disease resistance.This is the first attempt to characterize vWA gene family in plant species.
文摘BACKGROUND The elevation of plasma von Willebrand factor(vWF)has been proposed to be a predictor of lung cancer.Type 2 diabetes mellitus(T2DM)causes endothelial activation,resulting in the secretion of vWF.However,the role of vWF in patients with T2DM complicated with lung cancer remains unclear.AIM To investigate the clinical value of serum vWF as a tumor marker in patients with T2DM combined with lung adenocarcinoma in situ(AIS).METHODS This study enrolled 43 patients with T2DM combined with lung AIS(T2DM+AIS group),43 patients with T2DM alone(T2DM group),43 patients with lung AIS alone(AIS group),and 43 healthy volunteers(control group).The serum levels of vWF,insulin-like growth factor 1,and insulin-like growth factor binding protein 3 were determined.Multiple linear stepwise regression was performed to determine the correlations among variables.RESULTS Serum concentration of vWF in the T2DM+AIS group was significantly higher than those in the T2DM,AIS,and control groups(P<0.05).Serum vWF levels in the T2DM and AIS groups were significantly higher than that in the control group(P<0.05).There was no significant difference in serum vWF level between the T2DM and AIS groups.In the T2DM+AIS group,serum vWF was independently associated and positively correlated with serum levels of insulinlike growth factor 1 and insulin-like growth factor binding protein 3(P<0.05).CONCLUSION Serum vWF level may represent a novel biomarker for the early diagnosis of lung AIS.
基金Supported by a Grant From the Yen Tjing-Ling Medical Foundation
文摘AIM: To evaluate the correlations of plasma von Willebrand factor (vWF) level with the distant metastasis and prognosis of patients with colorectal cancer. METHODS: A total of 86 patients with histologically confirmed metastatic colorectal cancers receiving treatment at Taipei Veterans General Hospital were enrolled. All patients had measurable metastatic lesions and life expectancies of more than 3 mo. Plasma vWF levels were measured by immuno-turbidimetric assay and compared with results from 40 non-metastatic colorectal cancer patients and 22 healthy controls. Patients with metastatic colorectal cancer were divided into two groups according to serum vWF levels and the differences between these two groups were analyzed using x2 test. Data on age, gender, performance status, location of primary tumor, extent of metastasis, site of metastases, histological differentiation, serum CEA and plasma vWF levels were analyzed to determine association with survival. Survival curves were constructed by Kaplan-Meier product limit method and the data was analyzed using log-rank test on a microcomputer. Multivariate analysis using the Cox's proportional hazards regression model was then performed to determine the independent prognostic indicators among all of the possible variables.RESULTS: Colorectal cancer patients were identified as having significantly higher plasma vWF concentrations than healthy controls (P＜0.05). Moreover, higher vWF plasmalevels were associated with advanced tumor stage (P＜0.05) and the presence of multiple metastases (P = 0.014).Patients with lower vWF plasma levels (≤ 160%) survived significantly longer than those with a higher plasma vWF level (log-rank test, P = 0.0043). By multivariate analysis,plasma vWF levels (P＜0.001), the extent of metastasis (P = 0.012), and the performance status (P = 0.014)were identified as independent prognostic factors. CONCLUSION: Our data indicates that high plasma vWF concentrations correlate with advanced diseases and significantly poor prognosis of patients with metastatic colorectal carcinoma. It may serve as a potential biological marker of disease progression in these patients.
文摘AIM: To investigate the levels of D-dimer(DD) and vonWillebrand factor(vWF) and the relationship between DDand vWF in ulcerative colitis(UC) patients.METHODS: A total of 29 plasma specimens were obtainedfrom patients with ulcerative colitis (male 13, female 16),aged 21-47 years (33 + 11). Disease activity was assessed byTruelove-Writeria. Patients with a score of above 5 wereregarded as having active colitis. Twenty healthy people(male 12, female 8),aged 19-53 years(31 + 14), ssrved asnormal controls. Blood samples were taken from anantecubital vein puncture. Blood(1.8 mL) was injected intothe tubes containing sodium citrate (0. 13 mmol/L). Theplasma was obtained by centrifugation at 3000 r@ min-1 for 10min, and stored at -80 ℃ until assayed by ELISA.RESULTS: The mean plasma levels of DD and vWF in activeUC patients were significantly higher than those of thecontrols(0.69+0.41 vs0.27+0.11, P＜0.01;143+46 vs103 + 35, P ＜ 0.01 ). The mean plasma levels of DD in thepatients with active disease were higher than those withinactive disease(0. 69 + 0. 41 vs 0.48+0.29, P＜0.05). Thelevls of v WF were not different between active and inactivepatients. DD levels were positively related to vWF levels( r =0.574, P ＜ 0. 01 ). There was no significant differencebetween levels of DD and vWF and the scope of disease cndsex of the patients.CONCLUSION: vWF is an important feature and a goodmarker of UC; intravascular thrombus and endothelial celldysfunction were found in UC patients; and the combinedtest of DD and vWF is helpful to distinguish the activity ofthe UC patients.
基金supported by grants from National Natural Sciences Foundation of China(No.30672243,No.30671093)Natural Sciences Foundation of Hubei Province(No.ZR-Y1271)
文摘The present study examined von Willebrand factor (vWF) levels and ADAMTS13 activity in pregnant and severe preeclamptic women in order to shed light on the prothrombotic state in severe preeclampsia.Thirty healthy women of childbearing age,22 second trimester pregnant women,30 third trimester pregnant women and 10 severe preeclamptic patients were recruited in this study.ADAMTS13 activity was determined by the FRETS-vWF73 assay and vWF antigen (vWF:Ag) levels by an enzyme-linked immunosorbent assay.The results showed that there were statistically significant differences in plasma vWF antigen levels between the severe preeclamptic and third trimester pregnant women,between third and second trimester pregnant women (P<0.05).The third trimester pregnant women had significantly lower plasma ADAMTS13 activity than second trimester pregnant women (P<0.05).Nevertheless,no significant differences in plasma ADAMTS13 activity were found between severe preeclamptic patients and the third trimester pregnant women (P>0.05).In conclusion,plasma ADAMTS13 activity is normal in severe preeclampsia despite the increased vWF:Ag levels.Prothrombotic state is involved in the pathogenesis of severe preeclampsia,as a result of endothelial injury.
文摘AIM To evaluate the levels of von Willebrand factor(VWF) and metalloproteinase with thrombospondin type-1 motif, number 13(ADAMTS13) in inflammatory bowel disease(IBD) and correlate them with the disease activity.METHODS Consecutive patients with IBD aged 18 years or older were enrolled in the study. Forty-seven patients with ulcerative colitis(UC), 38 with Crohn's disease(CD), and 50 healthy controls were included. The white blood cell count, haematocrit, platelet count, fibrinogen, partial activated thromboplastin time, C-reactive protein, albumin, VWF antigen level(VWF:Ag), VWF ristocetin cofactor activity(VWF:RCo), VWF collagen-binding activity(VWF:CB), and ADAMTS13 antigen level(ADAMTS13:Ag) and activity(ADAMTS13act) were measured. The following ratios were assessed: V W F : R C o/V W F : A g, V W F : C B/V W F : A g, V W F : A g/ADAMTS13 act, and ADAMTS13act/ADAMTS13:Ag. RESULTS Compared to controls, the odds ratio(OR) of an elevated VWF: Ag > 150% was 8.7(95%CI: 2.7-28.1) in the UC group and 16.2(95%CI: 4.8-54.0) in the CD group. VWF:CB was lower in UC patients, and active CD was associated with a higher VWF: RCo(+38%). The ORs of VWF:CB/VWF:Ag < 0.7(a marker of acquired von Willebrand syndrome) in the UC and CD groups were 11.9(95%CI: 4.4-32.4) and 13.3(95%CI: 4.6-38.1), respectively. Active UC was associated with lower ADAMTS13:Ag(-23%) and ADAMTS13act(-20%) compared to UC in remission. Patients with active CD had a 15% lower ADAMTS13 act than controls. The activity of UC, but not that of CD, was inversely correlated with ADAMTS13:Ag(r =-0.76) and ADAMTS13act(r =-0.81). CONCLUSION Complex VWF-ADAMTS13-mediated mechanisms disturb haemostasis in IBD. A reduced WVF:CB is a risk factor for bleeding, while a lower ADAMTS13 level combined with an elevated VWF:Ag could predispose one to thrombosis.
文摘AIM: To evaluate the plasma von Willebrand factor (vWF) levels in patients with ulcerative colitis (UC) and to investigate their relationship with disease activity,systemic inflammation and coagulation activation.METHODS: In 46 patients with ulcerative colitis (active in 34 patients), clinical data were gathered and plasma vWF levels, markers of inflammation (ESR, CRP, and fibrinogen) and thrombin generation (TAT, F1+2, and D-dimers) were measured at baseline and after 12 wk of treatment. Plasma vWF levels were also determined in 52 healthy controls (HC). The relationship of plasma vWF levels with disease activity, disease extent, response to therapy, acute-phase reactants (APRs) and coagulation markers (COAGs) was assessed.RESULTS: The mean plasma vWF concentrations were significantly higher in active UC patients (143.38±63.73%) than in HC (100.75±29.65%, P = 0.001)and inactive UC patients (98.92±43.6%, P = 0.031).ESR, CRP and fibrinogen mean levels were significantly higher in active UC patients than in inactive UC patients,whereas there were no significant differences in plasma levels of D-dimers, F1+2, and TAT. UC patients with raised APRs had significantly higher mean plasma vWF levels than those with normal APRs (144.3% vs 96.2%,P = 0.019), regardless of disease activity. Although the mean plasma vWF levels were higher in UC patients with raised COAGs than in those with normal COAGs,irrespective of disease activity, the difference was not significant (141.3% vs 118.2%, P = 0.216). No correlation was noted between plasma vWF levels and disease extent. After 12 wk of treatment, significant decreases of fibrinogen, ESR, F1+2, D-dimers and vWF levels were noted only in UC patients with clinical and endoscopic improvement.CONCLUSION: Our data indicate that increased plasma vWF levels correlate with active ulcerative colitis and increased acute-phase proteins. Elevated plasma vWF levels in ulcerative colitis possibly reflect an acutephase response of the perturbed endothelium due to inflammation. In UC patients, plasma vWF levels may be another useful marker of disease activity or response to therapy.
文摘Increased thrombotic potential within the liver sinusoids due to local endothelial production of von Willebrand factor antigen macromolecules could represent an additional therapeutic target of portal hypertension in patients with cirrhosis. In this case, anti-inflammatory and antithrombotic drugs could modulate portal pressure by preventing the formation of intrahepatic platelet-induced microthrombi.
文摘BACKGROUND Many advanced hepatocellular carcinoma(HCC) patients are receiving sorafenib treatment. Sorafenib reportedly improves overall survival(OS) significantly in patients with HCC. Prediction of sorafenib response and prognosis in patients with HCC receiving sorafenib treatment are important due to the potentially serious side effects of sorafenib. A disintegrin-like and metalloproteinase with thrombospondin type-1 motifs 13(ADAMTS13) and von Willebrand factor(VWF) are associated with the pathophysiology of liver cirrhosis and HCC through their roles in hypercoagulability; they are also associated with angiogenesis via vascular endothelial growth factor(VEGF). The imbalance between ADAMTS13 and VWF was associated with prognosis of various cancers in patients undergoing chemotherapy.AIM To investigate ADAMTS13 and VWF as potential biomarkers for sorafenib response and prognosis in patients with HCC receiving sorafenib treatment.METHODS Forty-one patients with HCC receiving sorafenib treatment were included in this study. The initial daily sorafenib dose was 400 mg in all patients. ADAMTS13 activity(ADAMTS13:AC), VWF antigen(VWF:Ag), VEGF levels were determined by enzyme-linked immunosorbent assay. Univariate andmultivariate analyses were used to determine predictive factors for sorafenib response and prognosis in patients with HCC receiving sorafenib treatment.RESULTS ADAMTS13:AC was significantly higher in patients with stable disease(SD),partial response(PR), and complete response(CR) than in those with progressive disease(PD)(P < 0.05). In contrast, VWF:Ag and the VWF:Ag/ADAMTS13:AC ratio were significantly lower in patients with SD, PR, and CR than in those with PD(P < 0.05 for both). Multivariate analysis showed that the VWF:Ag/ADAMTS13:AC ratio was the only predictive factor for sorafenib response and ADAMTS13:AC was the only prognostic factor in patients with HCC receiving sorafenib treatment. The patients with a low ADAMTS13:AC(<78.0) had significantly higher VEGF levels than those with a high ADAMTS13:AC(≥ 78.0)(P < 0.05).CONCLUSION The VWF:Ag/ADAMTS13:AC ratio and ADAMTS13:AC are potentially useful biomarkers for sorafenib response and prognosis, respectively, in patients with HCC receiving sorafenib treatment.
文摘TO THE EDITOR
Cancer patients usually present a prothrombotic condition.Several clotting-related proteins, such as yon Willebrand factor (vWF), presenting higher plasma concentrations in these patients, may play a key role in this process. Moreover,some of those proteins are currently being characterized as response rate and overall survival markers in metastatic colorectal cancer (MCRC). In this comment article, we discuss the last piece of evidence that supports the use of vWF as a prognostic indicator in MCRC patients, provided by a paper recently published by Wang et al., in the World Journal of Gastroenterology. Summarizing, although vWF should be seriously considered as potential future prognostic and predictive indicator in colorectal cancer, more dynamic and better designed studies in longer series of patients should be conducted before standardizing its universal use among these patients.
文摘Objective: To explore the role of cytokines on the pathogenesis of atherosclerosis, and the lectins (Ps), von Willebrand (vWF), and D-dimer (D-D) in atherosclerosis (AS) patients. Methods: Sixtythree AS patients were randomly divided into the treated group ( n = 33, treated with TMJZ, 10 ml each time, three times a day) and the control group (n = 30, treated with Lovastatin, 10 mg, once daily). The levels of serum lipids (enzymatic methods), Ps, vWF, and D-D were measured before and after 8 weeks of treatment. Results: Serum total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), apo-protein B-100 (apoB-100) were significantly decreased (P＜0.05 or P＜ 0.01) and high-density lipoprotein cholesterol (HDL-C) was significantly raised (P＜0.05) after TM JZ treatment. Serum Ps,vWF, and D-D also declined (P＜0.05) after treatment. There was no significant difference between the treated and the control groups in these parameters except serum HDL-C level. Conclusion: TMJZ has good therapeutic effect in regulating serum lipids, improving endothelial cell function, inhibiting activation of platelets, and preventing the disturbance of blood coagulation/fibrinolysis function in patients with AS.
基金supported by grants from the National Science and Technology Major Project(2017ZX10203201)the opening foundation of the State Key Laboratory for Diagnosis and Treatmentof Infectious Diseases and Collaborative Innovation Center for Diag-nosis and Treatment of Infectious Diseases,First Affiliated Hospital,Zhejiang University School of Medicine(2015KF04)
文摘Recently the article“Perioperative von Willebrand factor dynamics are associated with liver regeneration and predict outcome after liver resection”was published in Hepatology[1].Prof.Starlinger et al.aimed to assess the association of von Willebrand factor(vWF)levels and clinical outcome in patients with liver cancers post-liver resection(LR).
文摘Background: Bleeding esophageal varices (OVs) due to portal hypertension are one of the major complications with high mortality in liver cirrhosis. So, early detection and management are mandatory. Aim: To evaluate the role of Von Willebrand factor (VWF) in predicting the presence of OVs. Patients and Methods: 62 patients with liver cirrhosis representing different Child-Pugh classes were included. The diagnosis of liver cirrhosis was based on the combination of clinical, laboratory and US examinations. All included patients underwent the following investigations: complete blood count, liver function tests (ALT, AST, serum bilirubin, albumin and total protein, prothrombin time (PT) and concentration (PC), INR and serum alkaline phosphatase), serum creatinine, Von Willebrand factor antigen (VWF-Ag) measurement and abdominal US. Upper endoscopic evaluation was done to detect presence or absence of varices (esophageal or gastric) and/or PHG. Results: 38 males and 24 females with their mean age (46 ± 12 years old) were included. Plasma Von Willebrand factor-Ag level was significantly higher in patients with OVs than those without varices (P value = 0.000). Also, its level was significantly higher in patients with higher grade of OVs, G3 than those with G1 or G2 (P value = 0.000). Patients with large OVs including those with G2 and G3 showed significantly higher values of VWF than those with small OVs (NO and G1) (P value = 0.000). VWF was independent predictor for detecting the presence of OVs with good sensitivity (90), specificity (77.3) and accuracy (85.5) at a cutoff value of 1.74 U/ml. Also it was an independent predictor for detecting the presence of large OVs with good sensitivity (91.2), specificity (85.7) and accuracy (88.7) at a cutoff value of 2.16 U/ml. Conclusion: VWF-Ag could be used as a non invasive laboratory independent predictor for the detection of OVs.
文摘von Willebrand factor (vWF) is an important compound in the human plasma. which is synthesized by endotlrelial cells and also by megakaryocytes. The gene for vWF is located near the tip of the short arm of chromosome 12, being approximately 180 kb in length and consisting of 52 exons separated by 51 introns. The mature vWF subunit consists of 2 050 amino acid residues with molecular weight of about 250 ku. In plasma vWF appears as various multimers. vWF has two well-characterized functions.
基金supported by the National Science Foundation of China ( 11772133, 11372116)the Fundamental Research Funds for the Central Universities ( HUST 0118012051)
文摘Von Willebrand Factor(VWF)is a concatameric glycoprotein that plays a key role in rapid hemostasis and thrombosis.VWF has different functional domains that can bind to various molecules such as collagen,hemostatic factorⅧ,integrin,and platelet glycoprotein lbα(GPlbα)to achieve multiple biological functions.During hemostasis,the A1 domain of VWF binds to GPIbαwhere platelets accumulate in the injured vascular endothelium.Due to forces generated by the hemodynamic gradient flow,the relations of bond-dissociation rates versus forces show that the lifetime of molecular bond has multiple states under the external force.We processed the experimental data of receptor-ligand in a single molecule obtained from optical tweezers by two different methods,including a Dudko-Hummer-Szabo equation,and another method combining force4ime history and force induced bond rupture.Then we used a recently developed physical equation regarding protein unfolding rate to fit our results.The lifetime of the bond between A1 and GPlbαobtained by the above mentioned two methods shows a'three-stage'change upon gradually increasing the external force.When the external force was below 8 pN,the lifetime of the bond deceased as the external force increased,which is a typical expression of a catch bond.The lifetime of the bond started to increase when the external force increased from 8 to 11 pN,and then decrease again when the external force increased to above 11 pN.Kim et al.used different processing methods and proposes a'flex-bond'model:the lifetime of the bond will decrease as the external force increases,then suddenly increase to a peak,and continue to decrease with the increase of force.A recently developed model based on the structural-elastic properties of molecules fits our data well,indicating that the bond formed by Al and GPlbαhas a catch-bond phenomenon in a certain interval of external forces,and a flex bond in other force intervals.In conclusion,A1-GPIbαbond will have a'slip-catch-slip'bond tendency.Our result provides a alternative understanding about the role of Al-GPlbαinteractions in the mechanism of hemostasis.
文摘Objectives: Bleeding from gastroesophageal varices is the most serious and life-threatening complication of cirrhosis and accounts for 10% of all cases of bleeding from the upper GI tract. It is essential to identify and treat those patients at the highest risk because each episode of variceal hemorrhage carries a 20 percent to 30 percent risk of death, and up to 70 percent of patients who do not receive treatment die within one year of the initial bleeding episode. The aim of this study is to determine the clinical predictors of bleeding esophageal varices and study the role of F VII (factor VII) and vWF (von willebrand factor) in predicting bleeding in patients with eosphogeal varices. Methods: A case control study was done on all patients with esophageal varices admitted at Sohag and Qena faculty of medicine hospitals from January 2012 to August 2013. Various clinical, laboratory and endoscopic variables were tested to determine the predictors of esophageal bleeding. Results: Among 300 patients with esophageal varices, 80 percent was due to hepatitis C virus (HCV), 18 percent was due to hepatitis B virus (HBV), and 2 percent had both HCV and HBV. As an etiologic factor for their liver disease, hemoglobin was 10.12 ± 2.26 g/l, platelet count 135.55 ± 65.94 × l09/l, prothrombin time 14.1 ± 0.92 second, albumin 2.88 ± 0.71 g/dl, ALT 48.25 ± 24.15 u/l, total bilirubin 1.92 ± 1.36 mg/dl. Factor VII was 27.4 ± 8.92 percent and vWF was 188.33 ± 13.66 IU/dl. Splenomegaly was reported 79.6 percent, 90.3 percent had ascites. 35 percent had grade III esophageal varices, 29 percent had four-column esophageal varices on endoscopy, 13.7 percent had concomitant gastric varices and 38.3 percent had portal hypertensive gastropathy. Platelet count, presence of red color sign, the number of columns of esophageal varices, presence of portal gastropathy on eosphagogastroduodenoscopy (EGD) showed a significant positive correlation with bleeding. There is a significant decrease of FVII and a significant increase of vWF in bleeding group in comparison with non bleeding group. Conclusion: Thrombocytopenia, presence of encephalopathy and endoscopic findings of large varices, presence of red color sign, and portal hypertensive gastropathy were found to be predictors of esophageal variceal bleeding. Increase of vWF and decrease of FVII are laboratory predictors of esophageal variceal bleeding.
基金the National Natural Science Foundation of China(81630027).
文摘Traumatic brain injury(TBI)-induced coagulopathy has increasingly been recognized as a significant risk factor for poor outcomes,but the pathogenesis remains poorly understood.In this study,we aimed to investigate the causal role of acrolein,a typical lipid peroxidation product,in TBI-induced coagulopathy,and further explore the underlying molecular mechanisms.We found that the level of plasma acrolein in TBI patients suffering from coagulopathy was higher than that in those without coagulopathy.Using a controlled cortical impact mouse model,we demonstrated that the acrolein scavenger phenelzine prevented TBI-induced coagulopathy and recombinant ADAMTS-13 prevented acrolein-induced coagulopathy by cleaving von Willebrand factor(VWF).Our results showed that acrolein may contribute to an early hypercoagulable state after TBI by regulating VWF secretion.mRNA sequencing(mRNA-seq)and transcriptome analysis indicated that acrolein over-activated autophagy,and subsequent experiments revealed that acrolein activated autophagy partly by regulating the Akt/mTOR pathway.In addition,we demonstrated that acrolein was produced in the perilesional cortex,affected endothelial cell integrity,and disrupted the blood-brain barrier.In conclusion,in this study we uncovered a novel pro-coagulant effect of acrolein that may contribute to TBI-induced coagulopathy and vascular leakage,providing an alternative therapeutic target.
