Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038454 (stroke)
147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Platelets are pivotal to the process of arterial thrombosis resulting in ischemic stroke. Occlusive thrombosis is initiated by the interaction of von Willebrand factor (vWf) and platelet glycoprotein (GP) Ibalpha. Three polymorphisms have been described in GP Ibalpha (Kozak T/C polymorphism, variable number of tandem repeats [VNTR], and the human platelet antigen 2a [HPA-2a] [Thr] or HPA-2b [Met] at position 145), each of which may enhance the vWf and GP Ibalpha interaction. This study investigated whether these polymorphisms are candidate genes for first-ever ischemic stroke. A hospital-based case-control study was conducted of 219 cases of first-ever ischemic stroke and 205 community controls randomly selected from the electoral roll and stratified by age, sex, and postal code. The subtypes of stroke were classified, the prevalence of conventional risk factors was recorded, and blood was collected to perform genotyping analysis for Kozak C or T alleles, VNTR, and HPA-2a/b. It was found that the Kozak T/C genotype was over-represented in the stroke group (32.2%) compared with controls (22.8%) (odds ratio [OR], 1.6; 95% confidence interval [CI], 1.03-2.54; P <.03), and the association was still present even after adjusting for conventional risk factors. There was a trend in the increased prevalence of HPA-2a/b in stroke patients (15%) compared with controls (9.9%) (adjusted OR, 1.8; 95% CI, 0.94-3.4; P =.07). No associations were seen with the VNTR polymorphism or with any of the polymorphisms with stroke subtype. It was concluded that the Kozak T/C polymorphism, which is associated with an increase in platelet GP Ibalpha surface expression, is an independent risk factor for first-ever ischemic stroke.
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PMID:Platelet glycoprotein Ibalpha Kozak polymorphism is associated with an increased risk of ischemic stroke. 1141 60

While the blood vessels are exposed to high pressures in hypertension, the main complications of hypertension (stroke and myocardial infarction) are paradoxically thrombotic rather than haemorrhagic. To investigate abnormalities of haemorheology (plasma viscosity, fibrinogen), endothelial dysfunction (von Willebrand factor), platelet activation (soluble P-selectin) and thrombogenesis (plasminogen activator inhibitor and fibrin D-dimer) in stroke and the effects of concurrent hypertension, we studied 86 consecutive patients (58 male, 28 female) aged < 75 years (mean age +/- SD, 64.2 +/- 9.2 years) with acute stroke (ictus < 12 h). Baseline blood tests on admission were compared with 46 'hospital controls' (patients with uncomplicated essential hypertension; mean age +/- SD, 65.9 +/- 3.8 years) and 24 healthy normotensive controls (mean age +/- SD, 65 +/- 14.0 years). Further comparisons were made between stroke patients with hypertension (systolic blood pressure > 160 mmHg and/or diastolic > 90 mmHg) on admission and those without hypertension. Mean plasma viscosity (one-way analysis of variance, P = 0.026) and fibrinogen levels (P = 0.016) were significantly higher in stroke patients and hospital controls, when compared with healthy controls. The von Willebrand factor, plasminogen activator inhibitor soluble P-selectin and fibrin D-dimer levels were highest in the acute stroke patients, intermediate in hospital controls and lowest in healthy controls (all P < or = 0.001). There were no significant differences in measured indices of haemorheology, endothelial dysfunction and thrombogenesis between the three stroke pathological subtypes (ischaemic/thrombotic, haemorrhagic or transient ischaemic attack). There were also no significant differences in the measured parameters for stroke patients with or without systolic blood pressure > 160 mmHg or diastolic blood pressures > 90 mmHg using clinical (manual) readings or mean daytime or night-time ambulatory blood pressure monitoring recordings. There were no statistically significant differences between the measured parameters on admission and at 3 months follow-up in 26 patients (all P = not significant). Plasma viscosity was significantly correlated with mean daytime systolic blood pressure (r = 0.314, P = 0.021) and mean night-time systolic blood pressure (r = 0.309, P = 0.025). This study of hypertension and haemostasis in acute stroke has demonstrated clear abnormalities of haemorheology, endothelial dysfunction, platelet activation and thrombogenesis, which do not appear to be affected by the height of the blood pressure or the presence of hypertension. This is despite the known hypercoagulable state found in hypertension and the relationship of haemostatic abnormalities to vascular complications.
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PMID:Abnormal haemorheology, endothelial function and thrombogenesis in relation to hypertension in acute (ictus < 12 h) stroke patients: the West Birmingham Stroke Project. 1146 15

The authors determined von Willebrand factor (vWF) in 63 persons with migraine, 11 persons with migraine and prior stroke, and 35 frequency-matched controls. Additional studies were done in a subset with migraine without aura who were headache free for >7 days. Migraineurs with prior stroke had significantly higher vWF antigen (170% versus 106%) and activity (162% versus 108%) than the control group. vWF antigen (126%) and activity (130%) were also significantly higher in migraineurs without stroke. Multimers and protease activity were normal in the interictal subset.
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PMID:Increased von Willebrand factor in migraine. 1146 24

To investigate gender differences in conventional, coagulation and fibrinolytic factors in South Asian ischaemic stroke patients, we compared these variables in 50 South Asian females (SAFP) with 90 South Asian males (SAMP) with ischaemic stroke and in 52 females (SAFC) and 38 males (SAMC) without stroke. Plasminogen activator inhibitor-1 (PAI-1) antigen levels were significantly higher in SAFP compared with SAMP (18.2 vs. 13.3 U/ml, P = 0.04) even after adjustment for known covariates, but there was no difference in PAI-1 antigen levels between males and females in the control group. South Asian females exhibited higher levels of factor VII antigen and FVII:C activity in both stroke patients (114 vs. 99% in males, P = 0.01; 116 versus 104% in males, P = 0.04) and controls (116 vs. 97% in males, P = 0.004; 115 vs. 93% in males, P = 0.01). There were no significant differences in the levels of fibrinogen (3.8 vs. 3.7 g/l), FXIIa (2.2 vs. 2.4 ng/ml), von Willebrand factor (1.8 vs. 1.9 IU/ml) and tissue plasminogen activator (11.4 vs. 12.0 ng/ml) in SAMP and SAFP respectively. These results suggest that South Asian females have increased FVII levels and that females with a history of ischaemic stroke have a decreased fibrinolytic potential in comparison with males.
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PMID:Decreased fibrinolytic potential in South Asian women with ischaemic cerebrovascular disease. 1147 61

Clinical significance of antibodies to phospholipids (aPL) and vascular endothelium (aVE) was evaluated in 20 patients (9 women and 11 men aged 36 +/- 10.8 years) with nodular polyarteritis (NP) corresponding to classification criteria of the USA Rheumatology College. Antibodies to cardiolipin (aCL) (IgG and IgM) and to beta 2-glycoprotein (beta 2-GP1) (IgG) were titered by solid-phase enzyme immunoassay. Total serum level of aVE (IgG + IgM + IgA) was measured by solid-phase enzyme immunoassay using Eahy. 926 endothelial hybrydoma cell culture. Anticardiolipin antibodies were detected in 11 (55%) of 20 patients, 3 of these had IgG aCL, 4 IgM aCL, and 4 both antibody isotypes. Serum titers of all aCL were moderate in all cases. No antibodies to beta 2-GP1 were detected in any of the patients. Total serum endothelial activity varied from 0 to 89.7% in patients with NP. Mean aVE level was 24.45 +/- 21.2%, which was significantly higher than in donors (p < 0.001). In 4 (26.7%) of 15 patients with NP total level of aVE surpassed the upper threshold normal value. The presence of aCL directly correlated with the presence of reticular livedo (r = 0.54, p < 0.05), but not with any other clinical laboratory manifestations of the disease, including thrombotic complications (deep thrombosis of lower limb veins, stroke, myocardial infarction), renal involvement, increased erythrocyte sedimentation rate, increased concentrations of von Willebrand factor antigen and C-reactive protein, or angiitis activity. Vascular endothelial antibodies directly correlated with renal involvement (r = 1.00, p < 0.01), distal gangrene of the limb (r = 0.83, p < 0.01), and angiitis activity (r = 0.78, p < 0.001), with high level of von Willebrand factor antigen and increased erythrocyte sedimentation rate (r = 0.66 and r = 0.64, respectively; p < 0.01), but not with aCL (r = 0.43, p > 0.05) of any isotype (aCL IgG r = -0.01; r = 0.34; p < 0.05). All patients with aVE had aCL in the serum (aCL IgG in 1, aCL IgG and IgM in 1, and aCL IgM in 2 patients). The results indicate different significance of a CL and aVE in NP; the mechanisms of realization of their pathogenetic potential are still to be investigated.
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PMID:[Antibodies to phospholipids and the vascular endothelium in nodular polyarteritis]. 1151 Jan 82

Abnormalities of coagulation and fibrinolysis may play an important role in the pathogenesis of ischaemic stroke and vascular dementia. We aimed to determine whether haemostatic function is altered in acute recent-onset or chronic ischaemic cerebrovascular disease. We studied consecutive patients with ischaemic stroke (n = 74) and vascular dementia (n = 42) compared with healthy controls (n = 40) in a case-control study. The ischaemic stroke group was assessed twice, 3-10 days after the acute stroke and at 1-3 months. Fibrinogen, fibrin D-dimer (marker of fibrin turnover) and von Willebrand factor (vWF) (marker of endothelial disturbance) were elevated acutely (P < 0.0001) and in the convalescent phase after ischaemic stroke (P < 0.0001, P < 0.0001, and P < 0.01 respectively, compared with controls). Similar results were seen in the vascular dementia group. Stepwise multivariate regression analyses showed that cerebrovascular disease correlated independently with fibrinogen (P < 0.001) and fibrin D-dimer levels (P < 0.001), while vWF correlated independently with electrocardiograph evidence of ischaemic heart disease (P = 0.004). Changes between acute and convalescent phases in ischaemic stroke were slightly inconsistent. However, in the acute stage there were tendencies for fibrinogen, D-dimer and vWF to be increased, and factor VIII was significantly higher. Abnormalities of haemostasis, including increased fibrin turnover and endothelial disturbance, are found in both acute and chronic cerebral ischaemia. Many of these patients have co-existent ischaemic heart disease and this may contribute to some of these changes. Acute ischaemic stroke is associated with transient changes in haemostatic factors; however, most abnormalities persist into the convalescent phase, and are also demonstrable in subjects with vascular dementia.
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PMID:Haemostasis in ischaemic stroke and vascular dementia. 1173 65

The von Willebrand factor (vWF) is a highly multimerized glycoprotein that promotes platelet adhesion and aggregation at a high shear rate, and also acts as a carrier of coagulation factor VIII. vWF has been identified as a risk factor for recurrent myocardial infarction in the general population. It has been reported that two polymorphisms of vWF gene promoter and the Thr789Ala polymorphism in vWF gene are associated with arterial thrombosis. The Sma I polymorphism is located in intron 2 of vWF gene. The relevance of this polymorphism to thrombotic disease was investigated by genotypic identification in two case-control studies: 107 patients with acute ischemic stroke, 49 patients with acute myocardial infarction (AMI), and 113 health controls age- and race-matched for each patient. Twenty-eight (26.2%) of the 107 patients with acute ischemic stroke, 8 (16.3%) of 49 patients with AMI, and 11 (9.7%) of 113 controls were found to be homozygous for CC genotype, respectively. The prevalence of the CC genotype in acute ischemic stroke was significantly higher than that of the normal controls (odds ratio [OR]=3.29, 95% confidence interval [CI]=1.54-7.01,.01>P>.001). However, the prevalence of the CC genotype in AMI was not significantly different from that of the normal controls (OR=1.81, 95% CI=0.68-4.82,.30>P>.20). Plasma vWF:Ag was also determined by enzyme-linked immunosorbent assay (ELISA) on the frozen plasma of 122 subjects. The mean plasma vWF:Ag levels of the controls, patients with acute ischemic stroke, and AMI were 0.468, 0.584, and 0.783 U/ml, respectively. The mean level of plasma vWF:Ag did not differ significantly between controls and patients with acute ischemic stroke (P=.195), but had significantly difference between controls and patients with AMI (P=.001). No association was found between the Sma I polymorphism and vWF plasma levels in controls, patients with acute ischemic stroke, or the AMI group (one-way ANOVA, P=.323, P=.315, P=.96). Results show that the Sma I polymorphism is strongly associated with increased risk of acute ischemic stroke, however, no association was observed between this polymorphism and AMI. This polymorphism of vWF may represent a newly identified risk factor for acute ischemic stroke in Chinese. Whether it is the real functional variant associated with acute ischemic stroke remains to be elucidated.
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PMID:The Sma I polymorphism in the von Willebrand factor gene associated with acute ischemic stroke. 1175 48

Vascular endothelial cells are critical participants in maintaining blood flow, with the ability to respond rapidly to injury. We have outlined above how the regulated secretion of a variety of hemostatic and inflammatory mediators contributes to these nearly instantaneous responses. The WPB are the most prominent of these regulated secretory granules, and there is growing evidence of additional granules that release their contents under a variety of conditions. The mechanisms responsible for the targeting of proteins to regulated secretory granules, and of exocytosis of these granules are being elucidated. EC appear to share some characteristics with other secretory cell types, but also are likely to have unique properties related to the storage and secretion of large multimeric proteins such as VWF and multimerin. Understanding these mechanisms may lead to new strategies for treating coronary artery disease, stroke, sickle cell disease, and hemophilia through drugs that modulate sorting and secretion, or by gene transfer approaches that introduce therapeutic molecules into the WPB for regulated release.
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PMID:Regulated secretion in endothelial cells: biology and clinical implications. 1181 99

The aim of the present study was to examine if soluble thrombomodulin (sTM) and von Willebrand factor (VWF) could predict a first-ever ischemic or hemorrhagic stroke. This study was an incident case-referent study from within a population-based cohort in northern Sweden. Up to 1996 about 44,000 subjects had been screened and stroke cases were classified according to the WHO MONICA criteria. A first-ever stroke occurred in 108 cases. A total of 216 controls were selected from the same cohort. This prospective study found no association with sTM or VWF and the development of a first-ever ischemic stroke (n = 87) in the logistic regression model. For the hemorrhagic stroke cases (n = 18), the multivariate logistic regression model revealed a significant negative association with sTM. When dichotomized, the upper level (>17.3 microg/L) of sTM, as compared with the lower level (<17.3 microg/L), showed one fifth of the risk for hemorrhagic stroke (OR, 0.18; CI, 0.05 to 0.69). No significant association was found for VWF. We suggest that the novel finding of an inverse relation between sTM and hemorrhagic stroke should be investigated in a larger study.
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PMID:Prospective study on soluble thrombomodulin and von Willebrand factor and the risk of ischemic and hemorrhagic stroke. 1185 79

We investigated whether circulating endothelial progenitor cells contribute to neovascularization after stroke. Donor bone marrow cells obtained from transgenic mice constitutively expressing beta-galactosidase transcriptionally regulated by an endothelial-specific promoter, Tie2, were injected into adult mice. Focal cerebral ischemia was induced by embolic middle cerebral artery (MCA) occlusion and changes of cerebral blood flow (CBF) were measured by perfusion-weighted magnetic resonance imaging (MRI). Laser scanning confocal microscopy (LSCM), immunohistochemistry and X-gal staining were performed. Perfusion-weighted MRI demonstrated increases in CBF around the boundary of an infarct area 1 month after ischemia. Morphological and 3-dimensional image analyses revealed enlarged and thin-walled blood vessels with sprouting or intussusception at the boundary of the ischemic lesion, which closely corresponded to elevated CBF areas detected on perfusion-weighted MRI, indicating the presence of neovascularization. X-gal and double immunostaining demonstrated that Tie2-lacZ-positive cells incorporated into sites of neovascularization at the border of the infarct, and these cells exhibited an endothelial antigenic marker (von Willebrand factor). In addition, bone marrow recipient mice without ischemia showed incorporation of Tie2-lacZ-expressing cells into vessels of the choroid plexus. These data suggest that formation of new blood vessels in the adult brain after stroke is not restricted to angiogenesis but also involves vasculogenesis and that circulating endothelial progenitor cells from bone marrow contribute to the vascular substructure of the choroid plexus.
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PMID:Bone marrow-derived endothelial progenitor cells participate in cerebral neovascularization after focal cerebral ischemia in the adult mouse. 1186 16


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