Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.4.15.1 (ACE)
18,300 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Insulin resistance has been implicated in the pathogenesis of essential hypertension. Studies from other countries discovered insulin resistance; in people with essential hypertension in was also associated with obesity, however, insulin resistance was found in lean people too. In obesity, insulin resistance occurs secondarily to many physiopathological states and circulating factors which adversely affects insulin action. The metabolic abnormality in this action was mainly found in relation to abdominal fat; in other cases, insulin resistance was found to be inherited. Hyperinsulinaemia can actually increase blood pressure and is associated with venous and arterial thrombosis and it also rises lipid levels. It is interesting too that insulin resistance and hyperinsulinaemia are associated with impaired fibrinolysis through high levels of fibrinogen and plasminogen activator inhibitor of endothelial type and in identifying individuals prone to myocardial infarction. Some antihypertensive drugs like beta-blockers, methyl-dopa and diuretics increase insulin resistance, while angiotensin converting enzyme-inhibitors have not shown any adverse metabolic affects. Alfa-1-blocker were beneficial and alfa-2-agonists were neutral, whereas calcium channel-antagonists are still in controversy. Treatment should be designed to improve the metabolic state; physical exercise, a diet rich in fruit, vegetable and rott vegetables, the reduction of abdominal fat and, finally, the use of antihypertensive drugs which decrease insulin resistance would be expected to reverse hyperinsulinaemia. Biguanides like metformin have also been found to reduce insulin resistance.
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PMID:[Insulin resistance: an etiological factor in essential arterial hypertension and coronary cardiopathy]. 792 20

Disturbances of the fibrinolytic system have been associated with cardiovascular disease and its risk factors. In the present study the effects of an ACE-inhibitor (enalapril) and a placebo on the fibrinolytic system have been compared. Eighty one survivors of acute myocardial infarction were randomised to treatment with enalapril or placebo. The mass concentrations and activity of tissue plasminogen activator (tPA) and plasminogen activator inhibitor (PAI-1) in plasma were measured three months after the infarction. The enalapril group had a significantly lower level of tPA antigen compared to the placebo-treated group (9.2 and 10.6 respectively). There was no difference between the two groups in any of the other fibrinolytic variables. We conclude that survivors of myocardial infarction treated with enalapril have a significantly lower concentration of tPA antigen than those treated with placebo. This may have a prognostic implication, as lower plasma concentrations of tPA antigen have been associated with better prognosis in patients with established coronary heart disease.
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PMID:Enalapril related changes in the fibrinolytic system in survivors of myocardial infarction. 835 88

Abnormalities in fibrinolysis, endothelial function, and glucose and lipid metabolism have been reported in hypertension. This study was conducted to examine the interrelationships between fibrinolytic factors, glucose and lipid metabolism, and endothelial function in hypertension. The effects of administering an angiotensin converting enzyme inhibitor, benazepril, were also examined. Blood levels of the following substances were measured in patients with borderline and mild hypertension (n=50, 51+/-19 years) and in age-matched controls (n=10): total cholesterol, triglycerides, tissue plasminogen activator activity and antigen, and plasminogen activator inhibitor type 1 activity and antigen. Insulin sensitivity was assessed by oral glucose tolerance test, and endothelial function was assessed by evaluating changes in diameter of the brachial artery during reactive hyperemia as observed by ultrasonography. Activities of tissue plasminogen activator and plasminogen activator inhibitor type 1 were both elevated in the hypertensive patients. Stepwise multiple regression analysis showed that plasminogen activator inhibitor type 1 antigen correlated with insulin sensitivity, total cholesterol levels, and triglycerides levels (P<.01). Endothelial function was negatively correlated with tissue plasminogen activator activity and antigen (P<.01). The chronic administration of benazepril (5-10 mg/d) for 20 weeks improved insulin sensitivity, endothelial function (6.6+/-3.4-->9.0+/-2.5%, P<.01), and tissue plasminogen activator activity and antigen. These results indicate that abnormalities in fibrinolysis are associated with endothelial dysfunction as well as disorders of glucose and lipid metabolism in patients with borderline and mild hypertension. The treatment of such patients with benazepril appeared to improve the impairment in fibrinolysis and endothelial dysfunction.
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PMID:Relationship between endothelial function and fibrinolysis in early hypertension. 945 23

Coronary heart disease (CHD) has been considered as a multifactorial disorder with the involvement of both environmental and genetic factors. The advent of tools to investigate individual variability of DNA has allowed us to perform the association studies of candidate genes. However, an association between genetic trait and phenotypic variations is not easy to demonstrate and several reported association between genetic markers and risk factors or overt CHD have gone unconfirmed. It should not be assumed that for a given genetic trait, the impact on risk will be similar in all populations. In particular, most studies of the molecular bases of CHD have involved Caucasian subjects, so much more work with the Korean population is needed before genetic testing for susceptibility to CHD can be offered to Koreans as a clinical service. In this review, we discuss two aspects of the molecular bases of CHD: i) Molecular bases of the candidate gene related to lipoprotein metabolism including apolipoprotein AI-CIII-AIV gene duster, apolipoprotein B, apolipoprotein E-CI-CII gene cluster, apolipoprotein(a), LDL receptors, lipoprotein lipase, cholesteryl ester transfer protein, and apo B editing protein; ii) Molecular bases of the candidate gene related to thrombotic and other factors including fibrinogen, factor VII, plasminogen activator inhibitor 1, homocysteine, stromelysin, paraoxonase, and angiotensin converting enzyme. Studies involving the Korean population, especially those performed by our teams, are also summarized.
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PMID:Molecular bases of coronary heart disease in Koreans. 953 12

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

Angiotensin converting enzyme inhibitors (ACE-I) are a mainstay for the treatment of heart failure, and of diabetic microalbuminuria. Recently ACE-I have been found to decrease plasma levels of circulating vascular cell adhesion molecule-1 (cVCAM-1) in patients with congestive heart failure. As increased cVCAM-1 levels are pathognomonic for diabetics with microangiopathy, we investigated the effects of ACE-I on plasma levels of cVCAM-1, intercellular adhesion molecule (cICAM-1), and cE-selectin in microalbuminuric diabetics. In addition, the effects of ACE-I on plasma levels of plasminogen activator inhibitor (PAI-1) and of tissue plasminogen activator (TPA) were studied. Fosinopril (10 mg/day) was administered over 12 weeks to 11 microalbuminuric patients with non-insulin-dependent diabetes mellitus (NIDDM). As expected, baseline plasma concentrations of cE-selectin, cICAM-1, and cVCAM-1 were markedly higher in patients than in healthy control subjects (n = 82; P < .001). PAI-1 levels in NIDDM were similar to those in control subjects, whereas TPA levels were about 25% lower in patients than in control subjects (P = .013). Serum levels of cVCAM-1 decreased by -19% (CI: -25% to -13%) after treatment with fosinopril (P = .003) and were no longer different from those of the control group. In contrast, plasma levels of cE-selectin, cICAM-1, PAI-1, and TPA were unaffected. As expected microalbuminuria decreased by -44% (CI: -65 to -22; P = .004). In conclusion, fosinopril lowered cVCAM-1 levels along with microalbuminuria in NIDDM. This may represent a novel mechanism of action of ACE-I in diabetes-associated endothelial dysfunction. Whether decreased VCAM-1 expression is responsible for the observed reduction in microalbuminuria, deserves further investigation.
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PMID:Fosinopril decreases levels of soluble vascular cell adhesion molecule-1 in borderline hypertensive type II diabetic patients with microalbuminuria. 1009 Mar 51

Do extremely old persons have a genetically favourable profile which has protected them from cardiovascular death? We have tried to answer this question by measuring DNA polymorphisms of selected cardiovascular risk indicators [factor VII, FVII (R/Q353, intron 7 (37bp)n, and -323ins10), beta fibrinogen (-455G/A), plasminogen activator inhibitor type 1, PAI-1 (-675(4G/5G)), tissue plasminogen activator, t-PA (intron 8 ins311), platelet receptor glycoprotein IIb/IIIa, GPIIb/IIIa (L/P33), prothrombin (20210G/A), methylene tetrahydrofolate reductase, MTHFR (A/V114), angiotensin converting enzyme, ACE (intron 16 ins287), and angiotensinogen (M/T235)]. Blood was collected from 187 unselected Danish centenarians, and 201 healthy Danish blood donors, aged 20-64 years (mean age 42 years). Genomic DNA was amplified using PCR and the genotype was determined by RFLP methods or allele-specific amplification followed by agarose gel electrophoresis. The frequencies of the high-risk alleles in centenarians were: for FVII R/Q353 0.91; for FVII intron 7 (37bp)n 0.67; for FVII-323 ins10 0.90; for fibrinogen 0.16; for PAI-1 0.52; for t-PA 0.59; for GPIIb/IIIa 0.16; for prothrombin 0.008; for MTHFR 0.33; for ACE 0.52; and for angiotensinogen 0.36. Comparable frequencies were observed in the blood donors. Subgroup analysis of men and women separately gave similar results. The genotype frequencies in the centenarians and the blood donors were similar for all polymorphisms, and this study suggests that common variations in genes associated with cardiovascular risk do not contribute significantly to longevity.
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PMID:Longevity is independent of common variations in genes associated with cardiovascular risk. 1049 71

As a class of therapeutic agents, the ACE inhibitors have proven to have long-term mortality benefit when used after myocardial infarction and among patients with symptomatic congestive heart failure. Clinical trial data also indicate that the use of ACE inhibitors is associated with reduced rates of recurrent coronary thrombosis, an observation that raises the possibility that the renin-angiotensin system may be directly involved in the thrombotic process and that the ACE inhibitors may have valuable fibrinolytic and/or antithrombotic effects. Recent in vitro and in vivo studies of angiotensin II and its interactions with the fibrinolytic system, particularly with the primary inhibitor of intravascular fibrinolysis, plasminogen activator inhibitor type 1 (PAI-1), provide substantial support for this hypothesis. In addition, a series of cross-sectional studies have described a genetic linkage between a common ACE gene polymorphism (DD) and the prevalence of clinical cardiovascular events, an intriguing finding as this polymorphism may account for much of the population variability in plasma ACE levels. Taken together, the totality of available clinical and experimental findings support the possibility of a direct linkage between the ACE system and vascular thrombosis that merits further prospective evaluation.
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PMID:Potential Antithrombotic and Fibrinolytic Properties of the Angiotensin Converting Enzyme Inhibitors. 1060 2

Experimental, genetic and clinical evidence suggests that the renin-angiotensin-aldosterone system (RAAS) may participate in the pathogenesis of thromboembolic cardiovascular disorders such as coronary heart disease. This interrelationship may involve mechanisms other than changes in arterial blood pressure. In addition to various possible interactions, accumulating evidence suggests that the RAAS is involved in the regulation of the fibrinolytic system. Several recent studies have shown that stimulation of the RAAS may be associated with an activation of plasminogen activator inhibitor 1 (PAI-1). Since profibrinolytic factors (especially tissue plasminogen activator [t-PA]) remain unchanged, increased activity of the RAAS may thus alter the fibrinolytic balance towards a decreased fibrinolytic activity. These findings may be of special importance for a variety of clinical problems such as the long-term effect of a low NaCl-intake on cardiovascular morbidity and mortality and the possible value of drugs indirectly or directly interfering with the RAAS such as diuretics, ACE-inhibitors and angiotensin II Type 1 (AT1) receptor antagonists.
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PMID:[Renin-angiotensin-aldosterone system and fibrinolysis]. 1119 56

Angiotensin converting enzyme (ACE) DD genotype, and plasminogen activator inhibitor (PAI-1) 4G/4G genotype have been reported to affect PAI-1 activity in control subjects and atherosclerotic patients, but no data are available on the influence of angiotensin II type 1 receptor (AT1R) A1166C polymorphism on the inhibitor levels. The degree of fibrinolytic activation after percutaneous transluminal coronary angioplasty (PTCA) has been found to affect the risk of restenosis. The aim of this study was to investigate the possible influence of ACE I/D, AT1R A1166C, and PAI-1 4G/5G polymorphisms on the changes of PAI-1 activity after primary successful percutaneous transluminal angioplasty. In 29 consecutive acute myocardial infarction patients, undergoing primary successful angioplasty, genotyping of ACE I/D, AT1R A1166C, and PAI-1 4G/5G polymorphisms was performed by polymerase chain reaction and restriction fragment length polymorphism analysis, and PAI-1 plasma activity (chromogenic method) was assessed before and after angioplasty. Following angioplasty, PAI-1 activity increased in 10 of 29 patients and decreased or remained unchanged in 19 of 29. ACE DD genotype was significantly (P = 0.04) associated with an increase of PAI-1 activity post angioplasty (OR DD/ID+II = 6.5, CI 95% 4.83-8.22). Whereas no effect of PAI-1 4G/5G and AT1R A1166C polymorphisms on PAI-1 response to angioplasty was demonstrated, these data suggest that renin-angiotensin system genes are involved in the regulation of the fibrinolytic response to balloon injury, possibly affecting angiotensin converting enzyme activity. This interaction between the renin-angiotensin system and hemostasis may be a mechanism by which ACE DD genotype affects the risk of restenosis after percutaneous transluminal angioplasty.
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PMID:Angiotensin converting enzyme DD genotype affects the changes of plasma plasminogen activator inhibitor-1 activity after primary percutaneous transluminal coronary angioplasty in acute myocardial infarction patients. 1128 8


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