Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The objective of this study was to describe associations of retinal arteriolar abnormalities with clinical and subclinical manifestations of atherosclerosis and a broad group of risk factors for vascular disease. A biracial population of 8772 adults (aged 48 to 72 years) living in 4 communities was examined from 1993 to 1995 were studied for that purpose. Retinal arteriovenous nicking and focal arteriolar narrowing were determined by light-box grading of a 45 degrees fundus photograph by use of a standardized protocol. Diameters of arterioles and venules were measured in digitized photographs, and a summary arteriolar-to-venular ratio was derived as an index of generalized arteriolar narrowing. Focal arteriolar narrowing was associated only with hypertension. Generalized arteriolar narrowing was associated with carotid plaque but not with any other evidence of atherosclerosis, either clinical (cardiovascular disease or stroke) or subclinical (carotid or popliteal artery thickness or lower limb obstructive disease), or with plasma cholesterol. It was also associated with smoking, with inflammatory markers (white blood cell count, fibrinogen, and reduced albumin), and with the triglyceride and high density lipoprotein cholesterol changes associated with inflammation. Arteriovenous nicking was inconsistently associated with subclinical atherosclerosis. It was not associated with cardiovascular disease, stroke, or plasma cholesterol. Arteriovenous nicking was associated with markers of inflammation and vascular endothelial dysfunction (von Willebrand factor and factor VIII). Arteriolar narrowing and nicking appear to be related to hypertension and inflammatory factors. Nicking may also be related to endothelial dysfunction. Results suggest that these arteriolar changes are pathologically distinct from atherosclerosis. Including their measurement in population studies may permit evaluation of the independent contribution of arteriolar disease to various ischemic diseases of the heart, brain, and other organs.
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PMID:Are retinal arteriolar abnormalities related to atherosclerosis?: The Atherosclerosis Risk in Communities Study. 1084 84

The mechanism behind the development of vascular complications of hypertension in the young human remains unclear. To explore the role of vascular endothelium-generated nitric oxide (a known mediator of leucocyte-platelet-endothelial interactions) in this context, we investigated markers of endothelial activation (soluble vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), P-selectin, E-selectin), and von Willebrand factor and the plasma level of the endogenous nitric oxide inhibitor asymmetric dimethyl arginine (ADMA) in a group of 31 (17 male, mean age 9.4 years) hypertensive and 9 (4 male, mean age 9.1 years) healthy, normotensive children and young adults. We found raised levels of ADMA (mean (SEM) 235 (32) n mol/l) and VCAM-1 (median (range) 1237 (675-2700) ng/ml) in the plasma of hypertensive subjects compared with those of normotensives (ADMA, 103 (7) n mol/l and VCAM-1, 1005 (425-1650) ng/ml, respectively). Furthermore, in hypertensive subjects, higher VCAM-1 concentrations (r = 0.66, p < 0.001) and vWF concentrations (r = 0.37, p = 0.04) were significantly associated with a higher plasma ADMA level. Therefore, an isolated increase in plasma VCAM-1 in hypertensives in association with raised ADMA may signify a selective "non-inflammatory" endothelial activation triggered by endothelial nitric oxide synthase inhibition. Since VCAM-1 is implicated in the origins of atherosclerosis, ADMA may be an important contributory factor in increasing the risk of atheroma formation in hypertensive children and young adults.
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PMID:Vascular endothelial cell activation associated with increased plasma asymmetric dimethyl arginine in children and young adults with hypertension: a basis for atheroma? 1085 1

Membrane-bound vascular cell adhesion molecule 1 (VCAM-1) allows the tethering and rolling of monocytes and lymphocytes as well as firm attachment and transendothelial migration of leukocytes. Soluble forms of VCAM (sVCAM-1) may serve as monitors of increased expression of membrane-bound VCAM-1 and thus may reflect progressive formation of atherosclerotic lesions. Levels of sVCAM-1 have been found to be increased among type 2 diabetic as compared with nondiabetic subjects. To study the association of plasma sVCAM-1 concentration and risk of cardiovascular and all-cause mortality among nondiabetic and diabetic subjects, we investigated an age-, sex-, and glucose-tolerance-stratified sample (n = 631) of a population-based cohort aged 50-75 years that was followed prospectively. Plasma levels of sVCAM-1 were determined in frozen -70 degrees C baseline samples. After 7.4 years (mean) of follow-up, 107 (17%) subjects had died (42 of cardiovascular causes). In the entire group, increased sVCAM-1 levels were significantly associated with increased risk of cardiovascular mortality (relative risks [RRs] per 100 ng/ml sVCAM-1 increase, 1.10 [1.05-1.15] after adjustment for age, sex, and glucose tolerance status). This RR was somewhat diminished by further adjustment for the presence of hypertension and cardiovascular disease; levels of total, HDL, and LDL cholesterol and homocysteine; the presence of microalbuminuria (a putative marker of endothelial dysfunction); levels of von Willebrand factor (a marker of endothelial dysfunction) and C-reactive protein (a marker of low-grade inflammation); and estimates of glomerular filtration rate. However, the RR remained statistically significant. The RR among type 2 diabetic subjects was 1.13 (1.07-1.20) per 100 ng/ml sVCAM-1 increase after adjustment for age and sex, which was somewhat higher but not significantly different from the RR in nondiabetic subjects (P value for interaction term, 0.12). Further adjustment for other risk factors gave similar results. In conclusion, levels of sVCAM-1 are independently associated with the risk of cardiovascular mortality in type 2 diabetic subjects and therefore might be useful for identifying subjects at increased cardiovascular risk. Increased plasma sVCAM-1 levels may reflect progressive formation of atherosclerotic lesions, or sVCAM-1 itself may have bioactive properties related to cardiovascular risk. Our data, however, argue against the hypotheses of sVCAM-1 levels simply being a marker of endothelial dysfunction, of low-grade inflammation, or of an impaired renal function.
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PMID:Increased levels of soluble vascular cell adhesion molecule 1 are associated with risk of cardiovascular mortality in type 2 diabetes: the Hoorn study. 1086 72

The aim of the present study was to investigate the effect of the treadmill electrocardiogram (TMECG) on thrombotic risk factors in hypertensive patients and normal individuals. Twenty patients, 10 males and 10 females between 40 and 55 years of age, were studied and twenty normal persons of matching sex and age were chosen as controls. Blood samples were obtained before and immediately after the TMECG. Platelet counts and function as well as fibrinogen and von Willebrand factor (vWF) levels were determined in each sample. A significant increase in platelet number and aggregation with collagen and ristocetin was observed in all groups after the TMECG. Fibrinogen and von Willebrand factor levels were also significantly increased in all individuals. It is known that platelets play an important role in the formation of thrombi and the enhancement in their number and activity, in certain circumstances, might favor the development of a thrombotic episode. Elevated fibrinogen concentrations are considered an independent cardiovascular risk factor. The above changes in patients with other predisponent factors for cardiovascular events, such as arterial hypertension, enhances the possibility of a vasooclusive episode. It is recommended therefore, that before suggesting a physical activity to a hypertensive patient, other parameters, such as age, previous training and the existence of other cardiovascular risk factors should be considered.
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PMID:[Effect of stress electrocardiogram on platelet function, concentration of von Willebrand factor and fibrinogen in hypertensive patients and healthy subjects]. 1096 Oct 46

Most clinical events associated with hypertension have a thrombotic component. Losartan is a selective, competitive antagonist of the thromboxane A2 receptor in experiments performed in isolated vascular strips and in human and rat platelet-enriched plasma. In this study, we investigated for the first time whether losartan at therapeutic doses has an effect on platelet aggregability and indexes of fibrinolysis in essential hypertensive subjects. Changes in the dose-response curve to platelet aggregation induced by the thrombin receptor-activating peptide SFLRRN-NH2 were determined in 9 patients (56% men, 72% white; mean age 52.8 years) with stage I or II essential hypertension and in 9 untreated healthy volunteers. After a 4-week washout period, hypertensive subjects received 2 weeks of placebo followed by 4 weeks of losartan 50 mg/day. Both subjects and end points were blinded for treatment assignment. In addition, plasminogen activator inhibitor type 1 antigen and von Willebrand antigen were studied in all patients and controls. Four weeks of losartan produced a statistically significant (p <0.05) increase in the concentration of SFLRRN-NH2 required to induce a half-maximal response in platelet aggregation extent and rate 4 weeks after initiation of treatment. The decrease in platelet aggregability was independent of blood pressure control and the effects of gender and age. Losartan had no effect on plasma concentrations of plasminogen activator inhibitor-1 and von Willebrand factor in hypertensive subjects. These data demonstrate for the first time a novel antiplatelet effect of losartan at therapeutic doses, which was independent of changes in blood pressure, plasma markers of fibrinolytic activity, and endothelial perturbation.
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PMID:Inhibition of platelet aggregability by losartan in essential hypertension. 1109 Jul 89

Alterations in the synthesis or enhanced inactivation of nitric oxide (NO) and an increase in endothelin-1 production lead to an imbalance that can induce arterial hypertension. Type II diabetes is characterized by impaired endothelium-dependent vasodilation and vascular disease. NO is produced through L-arginine pathway by three different isoforms of nitric oxide synthase (NOS), an inducible form that can be activated by cytokines such as tumor necrosis factor alpha (TNFalpha). We evaluated NO plasmatic levels, endothelial damage markers such as von Willebrand factor (vWF), platelet activation, soluble P-selectin (sP-Sel), TNFalpha levels, insulinaemia (I), glycosylated haemoglobin (HbA1c), glycaemia and blood pressure in 32 hypertensive diabetic type II patients (Group A), 37 hypertensive patients (Group B) and 35 healthy subjects (Group C) matched in sex, age, body mass index and dietary habits. The level of I was increased in patients compared to the controls and correlated with their NO levels. vWF plasmatic levels were increased in Group A compared to Groups B and C. We also found significant differences in platelet activation among all the groups. In diabetic patients, increased NO levels correlated with TNFalpha, HbA1c and platelet activation showed greater endothelial damage than in Group B. These parameters described a prothrombotic state associated with an insulin resistance state, an increased vWF release, raised sP-Sel and TNFalpha levels and, maybe, low NO bioavailability, which could lead to a higher risk of development of thrombotic events in hypertensive diabetic patients (Group A) than in the hypertensive patients in Group B.
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PMID:Endothelial dysfunction, nitric oxide and platelet activation in hypertensive and diabetic type II patients. 1132 20

To test the hypothesis that the hypercoagulable state in hypertension is significantly altered by anti-hypertensive therapy, we conducted a pilot prospective randomised double-blind trial of 40 untreated hypertensive patients (30 males, mean age 59 years) who were treated with either enalapril (10-20 mg per day) or losartan (50-100 mg per day) for 8 weeks. Thrombogenicity was assessed by measurement of plasma fibrinogen, soluble P-selectin (an index of platelet activation), plasminogen activator inhibitor 1 (PAI-1, an index of fibrinolysis) and von Willebrand factor (an index of endothelial dysfunction). Baseline von Willebrand factor alone was significantly higher in untreated hypertensive patients compared to controls (P<0.001). Following 8 weeks treatment with enalapril (mean dose 17 mg/day) or losartan (mean dose 77 mg/day), there was a significant reduction in mean blood pressure from 169+/-11/94+/-8 mmHg (baseline) to 147+/-14/84+/-7 mmHg (post-treatment) (P<0.001). However, there were no statistically significant changes in the levels of haemostatic markers (von Willebrand factor, fibrinogen, s-Psel and PAI-1). Our pilot study confirms previous observations of endothelial dysfunction in hypertensives. However, plasma fibrinogen and indices of platelet activation, fibrinolysis or endothelial dysfunction were not significantly affected by antihypertensive treatment with enalapril or losartan, despite satisfactory blood pressure control.
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PMID:Effect of antihypertensive therapy using enalapril or losartan on haemostatic markers in essential hypertension: a pilot prospective randomised double-blind parallel group trial. 1137 27

A previous study reported the ability of staphylococci to bind heparin and heparin-dependent host growth factors. The present study isolated and identified heparin- and basic fibroblast growth factor (bFGF)-binding surface components of S. epidermidis strain RP12 and S. haemolyticus strain SM 131. The staphylococcal heparin-binding component(s) were purified by affinity chromatography on heparin-Sepharose and a major heparin-binding protein, here designated HBP, was identified by immunoblot in these two coagulase-negative staphylococcal (CNS) species. The HBP was shown to be acidic with an approximate pI of 4.6 and a molecular mass around 17 kDa. The binding of heparin to HBP was inhibited by heparin, fucoidan, pentosan polysulphate and various other sulphated polysaccharides, but not by non-sulphated compounds. However, the purified HBP from both S. epidermidis and S. haemolyticus revealed broad specificity, and also bound bFGF, thrombospondin, von Willebrand factor and, weakly, fibrinogen. The N-terminal sequences of the 17-kDa HBP from S. epidermidis and S. haemolyticus showed only limited identity. Comparison of the first 15 amino acid residues derived from either strain with known sequences in the protein databases revealed no close similarities. Taken together, these results suggest that the adhesion of at least some CNS to host sulphated glycosaminoglycans may be mediated by a previously uncharacterised group of surface proteins.
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PMID:Isolation and characterisation of a 17-kDa staphylococcal heparin-binding protein with broad specificity. 1139 92

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 use of viral vectors for vascular gene therapy targeted at the endothelium is limited by the promiscuous tropism of vectors and nonspecificity of viral promoters, resulting in high-level transgene expression in multiple tissues. To evaluate suitable endothelial cell (EC)-specific promoters for vascular gene therapy, we directly compared the ability of the fms-like tyrosine kinase-1 (FLT-1), intercellular adhesion molecule-2 (ICAM-2), and von Willebrand factor (vWF) promoters to drive EC-restricted transcription after cloning into adenoviral vectors upstream of lacZ. Vastly different expression profiles were observed. Whereas both FLT-1 and ICAM-2 promoters generated transgene expression levels similar to cytomegalovirus in ECs in vitro, vWF expression levels were extremely low. Analysis of non-EC types revealed that ICAM-2 but not FLT-1 evoked leaky transgene expression, thus identifying FLT-1 as the most selective promoter. With an ex vivo human gene therapy model, the FLT-1 promoter demonstrated EC-specific transgene expression in intact human vein but no detectable expression from infected exposed smooth muscle cells in EC-denuded vein. Furthermore, when adenoviruses were systemically administered to mice, the FLT-1 promoter demonstrated extremely low-level gene expression in the liver, the major target organ for adenoviral transduction in vivo. This study highlights the potential of using the FLT-1 promoter for local and systemic human gene therapy in hypertension and its complications.
Hypertension 2001 Jul
PMID:Analysis of cell-specific promoters for viral gene therapy targeted at the vascular endothelium. 1146 61


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