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Neuroscience Bulletin 2021年第8期37卷 1160-1175页

作者： Wenxing Cui Xun Wu Dayun Feng Jianing Luo Yingwu Shi Wei Guo Haixiao Liu Qiang Wang Liang Wang Shunnan Ge Yan Qu Department of Neurosurgery Tangdu HospitalFourth Military Medical UniversityXi’an710038China

Traumatic brain injury(TBI)-induced coagulopathy has increasingly been recognized as a significant risk factor for poor outcomes,but the pathogenesis remains poorly *** 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 *** found that the level of plasma acrolein in TBI patients suffering from coagulopathy was higher than that in those without *** 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 *** 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 *** addition,we demonstrated that acrolein was produced in the perilesional cortex,affected endothelial cell integrity,and disrupted the blood-brain *** 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.

关键词： Traumatic brain injury Coagulopathy Autophagy Acrolein von willebrand factor

Serum von willebrand factor for early diagnosis of lung adenocarcinoma in patients with type 2 diabetes mellitus

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World Journal of Clinical Cases 2020年第10期8卷 1916-1922页

作者： Ying-Yi Zhou Xuan Du Jia-Li Tang Qiu-Ping Wang Ke Chen Bi-Min Shi Department of Endocrinology The First Affiliated Hospital of Soochow UniversitySuzhou 215000Jiangsu ProvinceChina Department of Thoracic Surgery The First Affiliated Hospital of Soochow UniversitySuzhou 215000Jiangsu ProvinceChina

BACKGROUND The elevation of plasma von willebrand factor(vWF)has been proposed to be a predictor of lung *** 2 diabetes mellitus(T2DM)causes endothelial activation,resulting in the secretion of ***,the role of vWF in patients with T2DM complicated with lung cancer remains *** 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 *** linear stepwise regression was performed to determine the correlations among *** Serum concentration of vWF in the T2DM+AIS group was significantly higher than those in the T2DM,AIS,and control groups(Pfactor 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.

关键词： Type 2 diabetes mellitus Adenocarcinoma in situ von willebrand factor Early diagnosis Correlation

Levels and activities of von willebrand factor and metalloproteinase with thrombospondin type-1 motif, number 13 in inflammatory bowel diseases

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World Journal of Gastroenterology 2017年第26期23卷 4796-4805页

作者： Dorota Cibor Danuta Owczarek Saulius Butenas Kinga Salapa Tomasz Mach Anetta Undas Department of Gastroenterology Hepatology and Infectious DiseasesJagiellonian University Medical College Department of Biochemistry College of MedicineUniversity of Vermont Department of Bioinformatics and Telemedicine Jagiellonian University Medical College Institute of Cardiology Jagiellonian University Medical College

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. METHODSConsecutive 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: VWF:RCo/VWF:Ag, VWF:CB/VWF:Ag, VWF:Ag/ADAMTS13act, and ADAMTS13act/ADAMTS13:Ag. RESULTSCompared 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 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 ADAMTS13act 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). CONCLUSIONComplex 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.

关键词： ADAMTS13 Inflammatory bowel disease Thrombosis Acquired von willebrand syndrome von willebrand factor

von willebrand factor Antigen and ADAMTS13 Activity Assay in Pregnant Women and Severe Preeclamptic Patients

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Journal of Huazhong University of Science and Technology(Medical Sciences) 2010年第6期30卷 777-780页

作者：张丹丹肖娟黄浩梁陈娟娟刘涛尹宗智高单萍刘琼艾继辉陈素华 Department of Obstetrics and Gynecology Tongji HospitalTongji Medical CollegeHuazhong University of Science and Technology Department of Obstetrics and Gynecology the First Hospital of Wuhan

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 *** healthy women of childbearing age,22 second trimester pregnant women,30 third trimester pregnant women and 10 severe preeclamptic patients were recruited in this ***13 activity was determined by the FRETS-vWF73 assay and vWF antigen (vWF:Ag) levels by an enzyme-linked immunosorbent *** 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 (P0.05).In conclusion,plasma ADAMTS13 activity is normal in severe preeclampsia despite the increased vWF:Ag *** state is involved in the pathogenesis of severe preeclampsia,as a result of endothelial injury.

关键词： von willebrand factor ADAMTS13 enzyme-linked immunosorbent assay fluorescence resonance energy transfer

Mutation in the leucinerich repeat of platelet glycoprotein Ibαresults in defects in its interaction with immobilized von willebrand factor under flow

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Chinese Medical Journal 2000年第8期113卷 21-26页

作者：董京飞 ChesterLi Alicia J.Schade Becky J.Fredrickson Lily Sun Larry V.McIntire José A.López From the Division of Hematology/Oncology Department of Internal Medicine Cox Laboratory for Bioengineering Rice University Houston TX 77030 USA Department of Molecular and Human Genetics Baylor College of Medicine and Veterans Affairs Medical Center Houston Cox Laboratory for Bioengineering Rice University Houston TX 77030 USA

OBJECTIVE: To characterize effects of the GP Ib alpha mutation (A156V) on its interaction with von willebrand factor (vWf) under high fluid shear stress. METHODS: The residue A156 of GP Ib alpha was converted to a valine and the mutant expressed in CHO cells expressing wild-type GP Ib beta and GPIX. The transfected cells were tested for their interaction with a panel of GP Ib alpha antibodies and for rolling on immobilized vWf under high shear. RESULTS: The mutation led to surface expression of a GP Ib alpha polypeptide that adopted a different conformation at its N-terminus because binding of the GP Ib alpha antibody AN51, which has a binding epitope in the N-terminal 35 residues, was eliminated, whereas binding of the others (AK2, MB45, and SZ2, all of which bind to regions C-terminal to the AN51 epitope) was normal. Mutant-expressing cells could adhere and roll on immobilized vWf under high fluid shear stress and rolled significantly faster than wild-type cells. CONCLUSION: These studies demonstrate that the mutation A156V results in a conformation change at the N-terminus of GP Ib alpha, which leads to an increase in the dissociation rate of the bond between the GP Ib alpha mutant and vWf.

关键词： mutation glycoprotein von willebrand factor defects

Elevated plasma von willebrand factor levels in patients with active ulcerative colitis reflect endothelial perturbation due to systemic inflammation

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World Journal of Gastroenterology 2005年第48期11卷 7639-7645页

作者： Petros Zezos Georgia Papaioannou Nikolaos Nikolaidis Themistoclis Vasiliadis Olga Giouleme Nikolaos Evgenidis Division of Gastroenterology Department of Haematology

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 ***: 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 ***: 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 ***: 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 e

关键词： Coagulation Endothelial injury Inflammation Inflammatory bowel disease Ulcerative colitis von willebrand factor

Specific inhibiting effects of Ilexonin A on von willebrand factor-dependent platelet aggregation under high shear rate

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Chinese Medical Journal 2004年第2期17卷 241-246页

作者：李敏吴伟康刘良廖福龙篠原幸人半田俊之介後藤信哉 School of Chinese Medicine Hong Kong Baptist University Kowloon Tong Hong Kong China Institute of Integrated Traditional Chinese and Western Medicine Sun Yat-Sen University Guangzhou 510080 China Institute of Chinese Material Medicine China Academy of Traditional Chinese Medicine Beijing 100700 China Department of Oriental Medicine Tokai University School of Medicine Kanagawa 259 - 1193 Japan Division of Cardiology Department of Medicine Tokai University School of Medicine Kanagawa 259 - 1193 Japan

Background llexonin A (IA), purified from the Chinese herbal medicine Maodongqing (Ilex pubescens Hook, et Am) has been commonly used in south China to treat thrombotic disorders. In this study, we aimed to study the inhibiting effects and mechanism of IA on von willebrand factor (vWF)-dependent high shear-induced platelet aggregation.Methods vWF-dependent high shear (10 800 s-1) induced aggregation of platelets obtained from normal donors in the presence or absence of IA was measured by a modified cone-plate viscometer and shear-induced vWF binding was measured by quantitative flowcytometry with monoclonal antibody known to bind exclusively to the C-terminal domain of vWF (LJ-C3) directly labeled with fluorescein isothiocyanate (FITC). P-selectin surface expression was also measured by a similar method with FITC conjugated anti-P-selectin monoclonal antibody (WGA1).Results Shear-induced platelet aggregation was inhibited by IA in a dose-dependent manner. The extent of aggregation decreased from (78. 6 ±4. 6)% in the absence of IA to (36. 5 ±2.1)% in the presence of IA (3. 3 mmol/L) (P<0. 0001, n =9) with a high shear rate of 10800 s-1. vWF binding and P-selectin expression were also inhibited by IA in a dose dependent manner. The number of binding FITC-LJ-C3 molecules increased after exposure of platelet-rich plasma to a high shear rate of 10800 s-1 for 6 minutes, but this shear-induced increased binding platelet surface vWF molecules and P-selectin expression can be decreased in the presence of IA.Conclusion vWF binding and vWF mediated platelet activation, aggregation occurring under high shear rate were inhibited by IA. IA may be a unique antithrombotic drug inhibiting the vWF-GP Ibα interaction, and may thus facilitate drug design targeting arterial thrombosis.

关键词： Ilexonin A platelet aggregation von willebrand factor P-selectin high shear rate

Significance of plasma von willebrand factor level and von willebrand factor-cleaving protease activity in patients with chronic renal diseases

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Chinese Medical Journal 2008年第2期121卷 133-136页

作者： LU Guo-yuan SHEN Lei WANG Zhao-yue GUO Xiao-fang BAI Xia SU Jian RUAN Chang-geng Department of Nephrology Jiangsu Institute of Haematology First Affiliated Hospital of Soochow University Suzhou Jiangsu 215006 China Department of Thrombosis and Haemostasis Jiangsu Institute of Haematology First Affiliated Hospital of Soochow University Suzhou Jiangsu 215006 China

Background von willebrand factor （vWF） mediates the initial capture of platelets to vascular subendothelium and is essential for platelet aggregation under high fluid shear stress as in arterial stenosis. On release from endothelial cells, vWF is rapidly cleaved by ADAMTS13/vWF-cleaving protease （vWF-CP）. We investigated the clinical significance of changes in plasma vWF and vWF-CP activities in chronic renal disease.Methods Plasma vWF and vWF-CP activities were measured using enzyme-linked immunosorbent assay （ELISA） and residual collagen binding assay respectively in patients with lupus nephritis （n=31）, primary nephritic syndrome （n=25）, diabetic nephropathy （n=45）, chronic glomerulonephritis （n=38） and 40 normal controls. The relation of their levels with pathological and renal status was analyzed.Results In all diseased patients the levels of vWF were significantly higher and vWF-CP activity significantly lower than the controls （both P〈0.01）. vWF in the four subgroups did not correlate with the stage of disease but correlated negatively with vWF-CP activity, vWF-CP activity was not changed two weeks after renal transplantation. Renal biopsy demonstrated that the vWF level in stage IV was higher than in stages II and III while vWF-CP activity was lower in patients with lupus nephritis. After eight-week treatment, the vWF level significantly decreased and the vWF-CP activity significantly increased in systemic lupus erythema, disease activity index 〈9, but not with index 〉9. Even though the vWF-CP activity was significantly lower in membranous nephropathy than in minimal change disease, mesangial proliferative glomerulonephritis or IgA glomerulonephritis, the vWF level was not significantly different. Conclusions The alterations of plasma vWF and vWF-CP activities were associated with different renal pathologies. Injury to endothelial cells and autoantibodies against vWF-CP activity may result in higher vWF level and lower vWF-CP activity in chronic renal

关键词： chronic renal disease von willebrand factor von willebrand factor-cleaving protease residual-collagen binding assay

BLOC-2 subunit HPS6 deficiency affects the tubulation and secretion of von willebrand factor from mouse endothelial cells

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Journal of Genetics and Genomics 2016年第12期43卷 686-693页

作者： Jing Ma Zhe Zhang Lin Yang Janos Kriston-Vizi Daniel F.Cutler Wei Lia Center for Medical Genetics Beijing Children's HospitalCapital Medical UniversityBeijing Pediatric Research InstituteMOE Key Laboratory of Major Pediatric Disease ResearchBeijing 100045China MRC Laboratory for Molecular Cell Biology University College of LondonLondon WCIE 6BTUK State Key Laboratory of Molecular Developmental Biology Institute of Genetics and Developmental BiologyChinese Academy of SciencesBeijing 100101 China Center of Alzheimer's Disease Beijing Institute for Brain DisordersBeijing 100069China

Hermansky-Pudlak syndrome（HPS） is a recessive disorder with bleeding diathesis, which has been linked to platelet granule defects. Both platelet granules and endothelial Weibel-Palade bodies（WPBs）are members of lysosome-related organelles（LROs） whose formation is regulated by HPS protein associated complexes such as BLOC（biogenesis of lysosome-related organelles complex）-1,-2,-3, AP-3（adaptor protein complex-3） and HOPS（homotypic fusion and protein sorting complex）. von willebrand factor（VWF） is critical to hemostasis, which is stored in a highly-multimerized form as tubules in the WPBs. In this study, we found the defective, but varying, release of VWF into plasma after desmopressin（DDAVP） stimulation in HPS1（BLOC-3 subunit）, HPS6（BLOC-2 subunit）, and HPS9（BLOC-1 subunit）deficient mice. In particular, VWF tubulation, a critical step in VWF maturation, was impaired in HPS6 deficient WPBs. This likely reflects a defective endothelium, contributing to the bleeding tendency in HPS mice or patients. The differentially defective regulated release of VWF in these HPS mouse models suggests the need for precise HPS genotyping before DDAVP administration to HPS patients.

关键词： Hermansky-Pudlak syndrome Weibel-Palade bodies von willebrand factor Biogenesis of lysosome-related organells complex Hemostasis

Clinical significance of plasma D-dimer and von willebrand factor levels in patients with ulcer colitis

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World Journal of Gastroenterology 2002年第3期8卷 575-576页

作者： XuG TianKL 等 DepartmentofGastroenterology ChinesePLA456HospitalofPLAJinan250031ShandongProvinceChina DepartmentofBiochemistry ShandongUniversityjinan250062ShandongProvinceChina

AIM: To investigate the levels of D-dimer(DD) and von willebrand factor(vWF) and the relationship between DD and vWF in ulcerative colitis(UC) patients. METHODS: A total of 29 plasma specimens were obtained from patients with ulcerative colitis (male 13, female 16) aged 21-47 years (33+/-11). Disease activity was assessed by Truelove-Writeria. Patients with a score of above 5 were regarded as having active colitis. Twenty healthy people(male 12, female 8) aged 19-53 years(31+/-14) served as normal controls. Blood samples were taken from an antecubital vein puncture. Blood(1.8 mL) was injected into the tubes containing sodium citrate (0.13 mmol/L). The plasma was obtained by centrifugation at 3000 ***(-1) for 10 min, and stored at -80 degrees until assayed by ELISA. RESULTS: The mean plasma levels of DD and vWF in active UC patients were significantly higher than those of the controls (0.69+/-0.41 vs 0.27+/-0.11, P<0.01 143+/-46 vs 103+/-35, P<0.01). The mean plasma levels of DD in the patients with active disease were higher than those with inactive disease(0.69+/-0.41 vs 0.48+/-0.29 P<0.05). The levels of vWF were not different between active and inactive patients. DD levels were positively related to vWF levels( r =0.574, P<0.01). There was no significant difference between levels of DD and vWF and the scope of disease and sex of the patients. CONCLUSION: vWF is an important feature and a good marker of UC intravascular thrombus and endothelial cell dysfunction were found in UC patients and the combined test of DD and vWF is helpful to distinguish the activity of the UC patients.

关键词： Adult Biological Markers Colitis, Ulcerative Female Fibrin Fibrinogen Degradation Products Humans Male Middle Aged von willebrand factor