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 highly organized histological architecture of the vascular wall and the specialized cellular phenotypes are perturbed in conditions such as atherosclerosis, restenosis, and hypertension. Alterations of endothelial cell (EC) phenotype in cardiovascular diseases (CVDs) as an effect of alteration of extracellular matrix (ECM) composition have not been well understood. In vitro study of EC phenotype is limited because they tend to dedifferentiate in subcultures. The objective of this study was to use in vitro cell culture on a biomimetic matrix model to characterize phenotype of human saphenous vein endothelial cells (HSVECs) harvested from CVD patients. Parameters studied were mRNA expression and synthesis of von Willebrand factor (vWF), plasminogen activation inhibitor (PAI), tissue plasminogen activator (t-PA), and endothelial nitric oxide synthetase (eNOS). Proliferation and apoptosis of HSVEC cultures obtained from eight different patients were compared on two matrices until passage 12. In early passages, both the prothombotic molecules vWF and PAI were overexpressed, whereas the antithrombotic molecules t-PA and eNOS were underexpressed. With increase in passage number, low expression of prothrombotic molecules and high expression of antithrombotic molecules were seen in cells on the model matrix. But when cells were grown on conventional gelatin-coated polystyrene, expression of prothrombotic molecules amplified further and antithrombotic molecules lessened with the progression of passages. On the model matrix HSVECs showed good proliferation rate and survival through several passages. It is demonstrated that matrix composition can influence switching of EC phenotypes into pro/antithrombotic states. This matrix model may be suitable to study the effect of exogenous factors on EC dysfunction with respect to CVD.
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PMID:Phenotype gradation of human saphenous vein endothelial cells from cardiovascular disease subjects. 1709 Apr 7

Obesity is a common disorder and related diseases such as diabetes, atherosclerosis, hypertension, cardiovascular disease and cancer are a major cause of mortality and morbidity in Western-type societies. Development of obesity is associated with extensive modifications in adipose tissue involving adipogenesis, angiogenesis and extracellular matrix proteolysis. The fibrinolytic (plasminogen/plasmin) and matrix metalloproteinase (MMP) systems cooperate in these processes. A nutritionally induced obesity model in transgenic mice has been used extensively to study the role of the fibrinolytic and MMP systems in the development of obesity. These studies support a role of both systems in adipogenesis and obesity; the role of specific members of these families, however, remains to be determined.
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PMID:Role of the fibrinolytic and matrix metalloproteinase systems in development of adipose tissue. 1717 99

According to current concepts, hypertension and hyperlipidemia cause vascular damage that leads to a hypercoagulative state. In this study, we investigated whether spontaneously hypertensive and hyperlipidemic rats (SHHR) can be a useful experimental model for complications in combined hypertension and hyperlipidemia, by comparing coagulative and fibrinolytic activities in SHHR with those in spontaneously hypertensive rats (SHR) and spontaneously hyperlipidemic rats (HLR). We measured coagulation and fibrinolysis markers in plasma and levels of fibrinogen and prothrombin mRNA in livers of eight-month-old male Wistar Kyoto rats (WKY), Sprague-Dawley rats (SD), SHR, HLR and SHHR. The plasma levels of fibrinogen in SHR, HLR and SHHR were significantly higher than those in WKY and SD, and were highest in SHHR. Higher plasma levels of antithrombin III and plasminogen were detected in increasing order in SHR, HLR and SHHR as compared to those in WKY and SD. Hepatic mRNA expressions of fibrinogen chains and prothrombin were enhanced in SHR, HLR and SHHR, resulting in increased plasma fibrinogen levels in SHHR. These results suggest that hypertension and hyperlipidemia can each cause hypercoagulation, with hyperlipidemia being a stronger factor than hypertension. Since a greater hypercoagulative state is a complication of combined hypertension and hyperlipidemia, the SHHR model is a good system for studying the early stage of atherosclerosis ensuing from hyperfibrinogenemia.
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PMID:Development of hyperfibrinogenemia in spontaneously hypertensive and hyperlipidemic rats: a potentially useful animal model as a complication of hypertension and hyperlipidemia. 1728 85

Obesity is a common disorder, and related diseases such as diabetes, atherosclerosis, hypertension, cardiovascular disease and cancer are a major cause of mortality and morbidity in Western-type societies. Development of obesity is associated with extensive modifications in adipose tissue involving adipogenesis, angiogenesis and extracellular matrix proteolysis. The fibrinolytic (plasminogen/plasmin) and matrix metalloproteinase (MMP) systems cooperate in these processes. A nutritionally induced obesity model in transgenic mice has been used extensively to study the role of the fibrinolytic and MMP systems in the development of obesity. These studies support a role of both systems in adipogenesis and obesity, and suggest that modulation of proteolytic activity may affect development of adipose tissue.
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PMID:Role of proteolysis in development of murine adipose tissue. 1827 77

In Alzheimer's disease (AD) Abeta accumulates because of imbalance between the production of Abeta and its removal from the brain. There is increasing evidence that in most sporadic forms of AD, the accumulation of Abeta is partly, if not in some cases solely, because of defects in its removal--mediated through a combination of diffusion along perivascular extracellular matrix, transport across vessel walls into the blood stream and enzymatic degradation. Multiple enzymes within the central nervous system (CNS) are capable of degrading Abeta. Most are produced by neurons or glia, but some are expressed in the cerebral vasculature, where reduced Abeta-degrading activity may contribute to the development of cerebral amyloid angiopathy (CAA). Neprilysin and insulin-degrading enzyme (IDE), which have been most extensively studied, are expressed both neuronally and within the vasculature. The levels of both of these enzymes are reduced in AD although the correlation with enzyme activity is still not entirely clear. Other enzymes shown capable of degrading Abetain vitro or in animal studies include plasmin; endothelin-converting enzymes ECE-1 and -2; matrix metalloproteinases MMP-2, -3 and -9; and angiotensin-converting enzyme (ACE). The levels of plasmin and plasminogen activators (uPA and tPA) and ECE-2 are reported to be reduced in AD. Reductions in neprilysin, IDE and plasmin in AD have been associated with possession of APOEepsilon4. We found no change in the level or activity of MMP-2, -3 or -9 in AD. The level and activity of ACE are increased, the level being directly related to Abeta plaque load. Up-regulation of some Abeta-degrading enzymes may initially compensate for declining activity of others, but as age, genetic factors and diseases such as hypertension and diabetes diminish the effectiveness of other Abeta-clearance pathways, reductions in the activity of particular Abeta-degrading enzymes may become critical, leading to the development of AD and CAA.
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PMID:Abeta-degrading enzymes in Alzheimer's disease. 1836 35

The combined therapy with enalapril and prolonged-release verapamil, as well as with enalapril and moxonidine significantly increases the level of antiatherogenic high-density-lipoprotein cholesterol, reduces the atherogenicity coefficients, decreases the concentrations of glucose, glycosylated hemoglobin, and soluble fibrinmonomeric complexes and the aggregation activity of thrombocytes, activates plasminogen in the blood of patients under conditions of metabolic syndrome with arterial hypertension. At the same time the enalapril monotherapy has no significant influence on the parameters of lipid and carbohydrate metabolism and the plasmatic and vascular-thrombocytic homeostasis.
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PMID:[The influence of antihypertensive agents on plasmatic and vascular-thrombocytic homeostasis in metabolic syndrome]. 1914 May 7

Patients on hemodialysis (HD) are prone to atherosclerotic cardiovascular complications. In an attempt to determine the significance of several atherosclerotic and thrombogenic parameters as risk factors for atherothrombotic cardiovascular disease (CVD) in these patients, we compared two groups of non-diabetic HD patients matched for age and sex, selected according to the absence (group 1, n = 30) or presence (group 2, n = 30) of symptomatic atherothrombotic vascular disease affecting the coronary, cerebral, or peripheral arteries. Duration of HD, primary renal disease (PRD), presence of hypertension, EPO treatment, and smoking habits were recorded. Serum total cholesterol (TC), triglycerides (TG), HDL-C, LDL-C, TC/HDL-C ratio, lipoprotein(a) (Lp(a)), fibrinogen (FG), plasminogen (PLG), fibronectin (FN), and hematocrit (HCT) were measured pre-HD in a midweek session. The same blood parameters were also assessed in twenty matched clinically healthy subjects (controls). None of the blood parameters differed between groups 1 and 2, except for serum Lp(a) and FN, which were higher in group 2 (p = 0.005 and p = 0.041, respectively). Both groups were not different regarding PRD, duration of HD, and EPO treatment, but the presence of hypertension and smoking habits were more common in group 2 (p = 0.008 and p = 0.045, respectively). Moreover, multiple stepwise logistic regression analysis with Lp(a), FN, hypertension, and smoking showed that the presence of hypertension (p = 0.016) and the Lp(a) (p = 0.027) and FN (p = 0.024) levels, but not smoking, were independent predictors for the presence of atherothrombotic CVD. Our results suggest that hypertension, abnormal lipid particles, and thrombogenic proteins may contribute to the high prevalence of CVD in HD patients.
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PMID:Cardiovascular risk factors in non-diabetic hemodialysis patients: a comparative study. 1921 4

The thrombin-activatable fibrinolysis inhibitor (TAFI) is a key mediator in the regulation of endogenous fibrinolysis, down-regulating clot lysis by degrading the C-terminal lysine residues from fibrin, which are important for binding and activating plasminogen. Elevated TAFI antigen levels have been suggested to be associated with promoter variants and the Ala147Thr polymorphism; increased TAFI stability and antifibrinolytic potential instead have been associated with the Thr325Ile polymorphism. We investigated the influence of these two polymorphisms on cardiovascular and thrombotic events in patients of the Ludwigshafen Risk and Cardiovascular Health (LURIC) study. The LURIC study is a prospective cohort study comprising more than 3,300 patients aimed at identifying biochemical and genetic markers for metabolic and cardiovascular diseases. We demonstrate that the Ile/Ile genotype at position 325 of TAFI associates with the incidence of stroke and the age at onset of first stroke in patients of the LURIC cohort. Both the incidence of stroke and the risk of a premature event are higher in TAFI Ile325Ile patients with predisposing risk factors for thrombotic events such as diabetes mellitus, myocardial infarction or hypertension, alone or in combination. In contrast, no significant association was identified for the TAFI Ala147Thr polymorphism. The robust association of the TAFI Thr325Ile polymorphism with the incidence and the age at onset of first stroke strongly suggests a key role for TAFI in the pathogenetic mechanism of stroke.
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PMID:Association between the Thr325Ile polymorphism of the thrombin-activatable fibrinolysis inhibitor and stroke in the Ludwigshafen Risk and Cardiovascular Health Study. 2021 89

Obesity is a common disorder, and related diseases such as diabetes, atherosclerosis, hypertension, cardiovascular disease and cancer are a major cause of mortality and morbidity in Westerntype societies. Development of obesity is associated with extensive modifications in adipose tissue involving adipogenesis, angiogenesis and extracellular matrix proteolysis. The fibrinolytic (plasminogen/plasmin) and matrix metalloproteinase (MMP) systems cooperate in these processes. Adipogenesis is tightly associated with angiogenesis, as shown by the findings that adipose tissue expiants trigger blood vessel formation, whereas in turn adipose tissue endothelial cells promote preadipocyte differentiation. A nutritionally induced obesity model in transgenic mice has been used extensively to study the role of the fibrinolytic and MMP systems and of angiogenesis in the development of obesity. Most studies support a role of these systems in adipogenesis and obesity, and suggest that their modulation may affect development of adipose tissue. Such models have also shown that treatment of obese female mice with estrogens has the potential to improve obesity, insulin resistance and glucose intolerance, via decreased expression of lipogenic genes. Thus, murine models of obesity have been very useful tools to study mechanisms of adipose tissue development, as well as effects of hormonal therapy.
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PMID:Murine models of obesity and hormonal therapy. 2126 32

Regulation of the fibrinolytic balance between plasminogen activators and inhibitors is modulated by the renin-angiotensin system (RAS). Impaired fibrinolytic function, characterized by increased plasminogen activator inhibitor type 1 (PAI-1) levels and decreased tissue plasminogen activator (t-PA) activity, has been found in patients with hypertension and may account in part for the increased risk of atherosclerosis and its clinical complications in these patients. In this regard, data from the literature indicate that different antihypertensive drugs may vary in their influence on fibrinolysis. Angiotensin-converting enzyme (ACE) inhibitors (ACE-I) have generally been shown to improve the fibrinolytic balance by reducing plasma PAI-1 levels. Calcium-channel blockers (CCB) have been reported to increase t-PA activity, and angiotensin receptor blockers (ARB) seem to be neutral in their effect. In the light of these data, this study aimed to compare the effects of ACE-I, ARB, and CCB on the fibrinolytic system in the early and late stages of the treatment in hypertensive patients. These data that the beneficial effect of RAS inhibition on fibrinolysis related to decrease in Ang II during early period of treatment. Amlodipine may also improve thrombogenic risk related to lowering the effect on increased platelet activation reflected by p-selectin. The greater improvement in the early and late stages of the fibrinolytic balance because of the combined action of RAS inhibition and Ca antagonism represents a further indication to the use of combinations of RAS inhibition (ACE-I or ARB) and CCB in the treatment of hypertension.
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PMID:Effects of lisinopril, irbesartan, and amlodipine on the thrombogenic variables in the early and late stages of the treatment in hypertensive patients. 2196 26


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