Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.23.15 (renin)
 35,795 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The metabolic and hemostatic effects of two oral contraceptives containing 150 mcg desogestrel and 20 mcg ethinyl-estradiol (EE) (MERCILON) or 30 mcg EE (MARVELON) were compared in order to examine the effect of reducing the EE dose in contraceptive pills. Forty-nine women participated in this randomized study during 6 cycles. In both groups, there was a significant increase in triglycerides, HDL-cholesterol and apoprotein A1; the same increase was observed for SBP and CBG. Slight and transient variations of fasting blood glucose levels were seen in the 30 mcg EE group and in the two groups for fasting insulin levels. The increase in renin substrate was significantly higher with the 30 mcg EE than with the 20 mcg EE pill. In both groups, plasminogen increased significantly, but antithrombin III, total and free protein S and fibrinogen decreased significantly only in women taking the 30 mcg EE pill, whereas there was no significant change in the 20 mcg EE group. Reducing the dose of EE in oral contraceptives from 30 mcg to 20 mcg minimizes their impact on renin substrate and hemostatic parameters.
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PMID:Hemostatic and metabolic effects of lowering the ethinyl-estradiol dose from 30 mcg to 20 mcg in oral contraceptives containing desogestrel. 822 50

Thromboembolic complications such as ischemic stroke and myocardial infarction are significantly more frequent in patients with arterial hypertension. From the available intervention studies, it appears that pharmacologic treatment of hypertension-at least with diuretics and beta-blockers-may more effectively protect against cerebrovascular as compared to coronary thromboembolic events. Whether other antihypertensive substances provide a more effective protection with respect to cardiac morbidity and mortality is the subject of numerous studies presently underway. These studies will help to answer the question of whether the extent of protection from coronary events during antihypertensive treatment depends on factors beyond blood pressure control. The fibrinolytic system is crucially involved in the pathogenesis of thromboembolic events. One determinant of this system is the balance between plasminogen activators (tissue-type plasminogen activator [t-PA]) and inhibitors (plasminogen activator inhibitor 1 [PAI-1]). Experimental and clinical evidence suggests that at least some of the drugs used in the treatment of hypertension may alter the activity of the fibrinolytic system. Scarce and controversial data with respect to such an interaction exist with respect to diuretics, beta-blockers, and calcium antagonists. In addition, experimental evidence demonstrates that PAI-1 is stimulated by angiotensin II (A II), whereas t-PA is activated by bradykinin. Thus, antihypertensive drugs acting within the renin angiotensin system should exert effects also within the fibrinolytic system. However, results from clinical studies with angiotensin converting enzyme (ACE) inhibitors and A II receptor antagonists do not unequivocally support such a concept. The discrepancy in the results may, at least in part, be explained by studies performed in healthy volunteer subjects showing that ACE inhibition profoundly affected fibrinolysis only during stimulation of the renin angiotensin system by NaCL restriction.
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PMID:Antihypertensive drug treatment and fibrinolytic function. 979 46

The plasminogen activator or fibrinolytic system is an important determinant of vascular homeostasis. It is one of the endogenous defence mechanisms against intravascular thrombus formation, which is implicated in the pathogenesis of myocardial infarction and other acute coronary syndromes. Reduced fibrinolytic activity is a risk factor for ischaemic cardiovascular events. The fibrinolytic system also contributes prominently to vascular remodelling. Fibrinolysis depends on a balance between plasminogen activators, such as urokinase and tissue-type plasminogen activator, and plasminogen activator inhibitor type 1. A growing body of evidence indicates that the renin-angiotensin system can disrupt the equilibrium of the fibrinolytic system both directly and indirectly, with clinical consequences. For example, it appears that angiotensin II and angiotensin i.v. increase the expression of plasminogen activator inhibitor type 1. Pharmacological interruption of the renin-angiotensin system with inhibitors of angiotensin-converting enzyme (ACE) exerts a positive influence on endogenous fibrinolytic balance by blocking the formation of angiotensin II and preventing the degradation of bradykinin. Recent data from our laboratory have provided additional evidence for a link between the renin-angiotensin system and the fibrinolytic system. These findings may help elucidate possible mechanisms by which ACE inhibition exerts vasculoprotective effects and reduces the risk of atherothrombotic events.
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PMID:Fibrinolytic balance, the renin-angiotensin system and atherosclerotic disease. 971 49

Polymorphisms of the renin-angiotensin system (RAS) have been shown to affect renal prognosis in a number of diseases. We examined the influence of deletion (D) and insertion (I) polymorphism in the angiotensin I-converting enzyme (ACE) gene and the other polymorphic markers of RAS, and that of plasminogen-activator inhibitor-1 (PAI-1) on renal scarring in reflux nephropathy. Ninety-four children with third- or fourth-degree reflux were the subject of the study. They were stratified into two groups according to the technetium-99m-dimercaptosuccinic acid (DMSA) findings: the first group consisted of 41 patients with no scar formation. In the second group (n = 53), there was significant scar formation in the refluxing units. ACE levels, ACE gene, angiotensin-1 receptor (AT1) A1166C, angiotensinogen (ATG) M235T, and PAI-1 4G/5G polymorphisms were studied. In the second group with scarred kidneys, 18 patients had decreased renal function. The frequency of patients homozygous for the D allele was significantly greater in the second group with scar formation in the refluxing units compared with the first group of patients (P < 0.005). On multivariate analysis, the DD genotype was the only factor that had a significant impact on renal scar formation, introducing a 4.9-fold risk (P < 0.05, 95% confidence interval). We were unable to find any correlation with the presence ofDD genotype and hypertension, decreased renal function, proteinuria, or sex of the patient. DDgenotype correlated with the serum ACE levels (P < 0.005). AT1and ATGpolymorphisms and PAI-1 polymorphism did not correlate with scar formation or any of the parameters. This study provides evidence that the DDgenotype of ACE may be a genetic susceptibility factor contributing to adverse renal prognosis in reflux nephropathy; namely, scar formation. The role of the synergism between the aforementioned genetic polymorphisms can be enlightened with larger patient groups, possibly through multicenter studies.
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PMID:Implications of certain genetic polymorphisms in scarring in vesicoureteric reflux: importance of ACE polymorphism. 1040 Oct 28

Twenty-four Japanese hypertensive patients of both sexes, grouped as having 'medium' and 'high' baseline total lipid values, had their serum lipids, lipoproteins and plasma fibrinolytic parameters, renin and noradrenaline levels determined after 3 months of amlodipine treatment. For the patients with 'medium baseline values', total plasminogen activator inhibitor-1 (PAI-1) and t-PA-PAI-1 complex levels decreased, while the changes in lipids and lipoproteins were not significant after amlodipine treatment. For the patients with 'high baseline values', the mean triglyceride and very low density lipoprotein cholesterol (VLDLC) levels were reduced while the reductions in total and free PAI-1 and the increase in tissue plasminogen (t-PA) levels were not significant after amlodipine treatment. Negative correlations were observed between t-PA and high density lipoprotein cholesterol (HDLC) and HDLC/total cholesterol (TC) ratio in the patients with 'medium baseline values' while t-PA positively correlated with HDLC/TC ratio in patients with 'high baseline values'. The mean levels of renin and noradrenaline remained unchanged before and after amlodipine treatment in the two baseline groups. These findings show that baseline lipid levels of the hypertensive patients could influence lipids and fibrinolytic parameters differently during amlodipine treatment. The baseline lipid levels also influenced the metabolic association between lipids and fibrinolytic function in hypertensive patients during amlodipine treatment. The baseline total lipid values could therefore provide explanations for the complex metabolic interaction between lipids and fibrinolytic function as well as for the antiatherogenic actions of amlodipine treatment in hypertensive patients.
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PMID:Influence of baseline values on lipids, lipoproteins and fibrinolytic parameters during amlodipine treatment of hypertension in Japanese patients. 1060 Feb 72

Twenty-four Japanese hypertensive patients of both sexes, grouped as having 'medium' and 'high' baseline total lipid values, had their serum lipids, lipoproteins and plasma fibrinolytic parameters, renin and noradrenaline levels determined after 3 months of amlodipine treatment. For the patients with 'medium baseline values', total plasminogen activator inhibitor-1 (PAI-1) and t-PA-PAI-1 complex levels decreased, while the changes in lipids and lipoproteins were not significant after amlodipine treatment. For the patients with 'high baseline values', the mean triglyceride and very low density lipoprotein cholesterol (VLDLC) levels were reduced while the reductions in total and free PAI-1 and the increase in tissue plasminogen (t-PA) levels were not significant after amlodipine treatment. Negative correlations were observed between t-PA and high density lipoprotein cholesterol (HDLC) and HDLC/total cholesterol (TC) ratio in the patients with 'medium baseline values' while t-PA positively correlated with HDLC/TC ratio in patients with 'high baseline values'. The mean levels of renin and noradrenaline remained unchanged before and after amlodipine treatment in the two baseline groups. These findings show that baseline lipid levels of the hypertensive patients could influence lipids and fibrinolytic parameters differently during amlodipine treatment. The baseline lipid levels also influenced the metabolic association between lipids and fibrinolytic function in hypertensive patients during amlodipine treatment. The baseline total lipid values could therefore provide explanations for the complex metabolic interaction between lipids and fibrinolytic function as well as for the antiatherogenic actions of amlodipine treatment in hypertensive patients. 2000 Academic Press@p$hr Copyright 2000 Academic Press.
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PMID:INFLUENCE OF BASELINE VALUES ON LIPIDS, LIPOPROTEINS AND FIBRINOLYTIC PARAMETERS DURING AMLODIPINE TREATMENT OF HYPERTENSION IN JAPANESE PATIENTS. 1071 29

Vascular disease is a multifactorial disease that involves atherosclerotic and thrombotic factors. Genetic polymorphisms have been associated with myocardial infarction and angina pectoris. The aim of the present study was to assess the relationship between some genetic polymorphisms and myocardial infarction (MI) or vasospastic angina pectoris in a population from southern France. Genetic polymorphisms of the renin angiotensin system (the D/I polymorphism of the ACE gene and the A1166C polymorphism of the angiotensin II type 1 receptor [AT1R]) and of haemostatic factors (the -675 4G/5G polymorphism of the plasminogen-activator inhibitor 1[PAI-1] gene, and the G to T common point mutation in exon 2, codon 34 of the Factor XIII A-subunit gene) were examined. We assessed the genotype distribution in consecutive coronary artery disease (CAD) patients with MI (n = 201) and vasospastic angina pectoris (n = 43) and in 244 healthy controls comparable in age, sex, body mass index and total cholesterol level. The genotype distribution of AT1R polymorphism was significantly different between controls and patients, the prevalence of the C allele carriers being higher in patients with MI after the age of 45 than in control individuals (61 vs 45%, p <0.01), leading to an odds ratio (OR) of 2 (CI: 1.2-3.4). When looking at the group of patients with vasospastic angina the difference was even higher (76 vs 45%, p <0.01) yielding an OR of 4.3 (CI: 1.4-17.4). Genotype distributions of ACE, PAI-1 and Factor XIII polymorphisms were similar in patients and in controls. This study is in favor of a role of ATIR gene polymorphism in myocardial infarction and vasospastic angina.
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PMID:Genetic polymorphisms and coronary artery disease in the south of France. 1073 75

Reduced activity of the endogenous fibrinolytic system contributes to intramural deposition of microthrombi in atherogenesis and to intraluminal deposition of thrombi leading to acute complications of atherosclerosis such as acute coronary syndromes. Endogenous fibrinolytic activity is predominantly regulated by the plasminogen activator inhibitor type 1 (PAI-1). Increased activity of PAI-1 leading to reduced endogenous fibrinolytic activity has been identified as an important independent risk factor for cardiovascular disease. Vascular endothelial cells form a barrier between the circulating blood with its dynamic balance between ongoing thrombosis and fibrinolysis and the subendothelial layers of the vascular wall with their prothrombotic activity. In addition, endothelial cells synthesize and secrete substantial amounts of plasminogen activators and their inhibitor PAI-1. Thus, endothelium plays an important role in the regulation of endogenous fibrinolysis. After describing the components of the endogenous fibrinolytic system and its interactions, this review focuses on the impact on endogenous fibrinolysis by the renin angiotensin system, the kallikrein kinin system, and type 2 diabetes mellitus. Investigations using transgenic and knock-out animal models--the results of which are also summarized--have improved our understanding of the interaction between endogenous fibrinolysis and endothelium. In each section of the review therapeutic implications and potentials are discussed.
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PMID:[Endothelium and endogenous fibrinolysis]. 1079 78

Angiotensin-converting enzyme (ACE) inhibitors and angiotensin II type 1 (AT1) receptor blockers share a number of common properties, including their ability to lower blood pressure. However, they can be differentiated based on their individual effects on the renin-angiotensin system, the fibrinolytic system and the actions of bradykinin. They act at different points in the cascade of events that constitute the renin-angiotensin system. In animal models of atherosclerosis, ACE inhibition was associated with a significant reduction in the percentage surface area of lesions, while no similar effect was evident with AT1 receptor blockade. In the fibrinolytic system, both ACE inhibition and AT1 receptor blockade were associated with reduced aldosterone levels, although the effect was greater with ACE inhibition; only ACE inhibition was associated with a significant reduction in plasminogen activation inhibitor-1. By blocking the degradation of bradykinin, ACE inhibitors potentiate the ability of bradykinin to reduce blood pressure and stimulate the release of tissue-type plasminogen activator from the vasculature, an effect not seen with AT1 receptor blockers.
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PMID:Pharmacology of ACE inhibitors versus AT1 blockers. 1090 25

Fibrinolysis is controlled by the plasminogen activator system. The proteolytic activity of this system is mediated by plasmin, which is generated from plasminogen by one of two plasminogen activators. Plasminogen activator inhibitor-1 (PAI-1) inhibits this process. Individuals with reduced fibrinolytic activity are at increased risk for ischemic cardiovascular events, and reduced fibrinolysis may underlie some of the pathological consequences of reduced nitric oxide (NO) availability. Within the vasculature, angiotensin II stimulates the release of PAI-1, thereby reducing fibrinolytic activity. Thus, the plasminogen activator system is largely controlled by the renin-angiotensin system (RAS). In accordance with this finding, treatment with angiotensin converting enzyme (ACE) inhibitors is associated with substantial reductions in the incidence of ischemic cardiovascular events. Links between the RAS, fibrinolytic balance, and cardiovascular pathology are further supported by evidence from transgenic and knockout animal models. This article discusses the role of the plasminogen activator system in cardiovascular pathology, and the potential for alleviating that pathology by manipulation of the RAS.
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PMID:Angiotensin and vascular fibrinolytic balance. 1182 73


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