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)

The heart is composed of highly differentiated cardiac myocytes, which constitute parenchyma, and stroma or connective tissue. Fibrillar collagen turnover in the heart and its valve leaflets, in particular, is dynamic and essential to tissue repair. Emerging evidence further suggests connective tissue is a metabolically active entity, where peptide hormones are generated and degraded and, in turn, these peptides regulate collagen turnover. This concept arose from quantitative in vitro autoradiography using an iodinated derivative of lisinopril (125I-351A) as ligand to localize angiotensin converting enzyme (ACE) binding density within the heart. A heterogeneous distribution was found: low-density ACE binding within atria and ventricles; high ACE binding density at sites of high collagen turnover, such as valve leaflets, adventitia, and fibrous tissue of diverse etiologic origins. ACE-producing cells at these latter sites were identified by monoclonal ACE antibody. They included valvular interstitial cells (VIC) and fibroblast-like cells each of which also contained alpha-smooth muscle actin and the transcript for type I collagen (in situ hybridization). Substrate utilization in cultured VIC was found to include angiotensin I and bradykinin. Angiotensin II and bradykinin receptor-ligand binding was observed in VIC and at fibrous tissue sites. Connective tissue ACE is independent of circulating angiotensin II. In vivo, fibrous tissue formation is attenuated by ACE inhibition or antagonism of AT1 receptor. Angiotensin II and bradykinin are stimulatory and inhibitory, respectively, to cultured adult cardiac fibroblast collagen synthesis suggesting a paradigm of reciprocal regulation to fibroblast collagen turnover. Stroma and its cellular constituents represent a dynamic metabolic entity that regulates its own peptide hormone composition and turnover of fibrillar collagen. These findings may provide insights that could be used to advantage to either promote or forestall fibrous tissue formation depending on the nature of cardiovascular disease.
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PMID:Connective tissue and repair in the heart. Potential regulatory mechanisms. 775 73

Microalbuminuria indicates slightly elevated urinary albumin excretion. In most cases, microalbuminuria is of glomerular origin and indicates initial glomerulosclerosis. Microalbuminuria has a high predictive value for nephropathy in insulin-dependent diabetes subjects and for premature mortality due to cardiovascular disease in non-insulin-dependent diabetes subjects and in the general population. All cardiovascular risk factors can be determinants for microalbuminuria constitution, especially the genetic determinants of these risk factors. Thus, microalbuminuria can be an indicator to summarize renal or cardiovascular risk, or both, in various populations. Treatment interventions were performed using microalbuminuria as the endpoint. So far, the most convincing results were obtained with angiotensin I-converting enzyme inhibitors to prevent nephropathy in insulin-dependent diabetes subjects.
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PMID:Microalbuminuria. 780 56

The ACE gene has recently been shown to be associated with myocardial infarction, especially in subjects considered at low risk for coronary heart disease (CHD) according to common classification criteria. The possible relationship between deletion polymorphism in this gene and CHD risk factors, as well as asymptomatic extracoronary atherosclerosis, has been investigated in the present study. One hundred and seventy-four subjects, enrolled in a cardiovascular disease prevention study, underwent clinical and biochemical examination and ACE-I/D polymorphism determination. Subjects > 45 years of age (n = 107) also received echo-Doppler examination of the carotid arteries. Based on the results of ACE-I/D polymorphism, subjects were divided into three groups: homozygous for deletion (D/D), homozygous for insertion (I/I) and heterozygous (I/D). The prevalence of CHD risk factors as well as of extracoronary atherosclerosis was similar in the three genotype groups. Similarly, there was no association between the presence of atherosclerotic lesions and genotype in subjects at low and high CHD risk. Ten subjects with diabetes mellitus had ACE-D/D genotype. Among these subjects seven had hypertension. Eight subjects with diabetes mellitus had ACE-I/D genotype and only one of these was hypertensive. None of the ACE-I/I subjects was diabetic. ACE-I/D polymorphism seems to play a role in the development of hypertension, at least in diabetic subjects. Its determination may help to identify and monitor diabetic subjects prone to hypertension.
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PMID:Association between ACE-D/D polymorphism and hypertension in type II diabetic subjects. 780 99

GROWTH-PROMOTING EFFECTS OF ANGIOTENSIN: Angiotensin, a vasoconstrictive peptide, is now known to be an agent of vascular and cardiac growth and may directly influence the pathophysiology of coronary artery disease and ventricular remodeling. Vascular growth occurs when angiotensin activates autocrine and paracrine growth factors, including fibroblast growth factor, transforming growth factor beta-1 and platelet-derived growth factor, and is modulated by endothelium-derived vasodilators and growth inhibitors. ANGIOTENSIN AND CARDIOVASCULAR DISEASE: The presence of angiotensin converting enzyme (ACE) and angiotensin II has been demonstrated in vascular tissue, and these local substances are causally involved in the development of vascular lesions. Similarly, angiotensin can stimulate cardiac myocyte growth and matrix modulation. Cardiac tissue ACE is implicated in ventricular remodeling in the course of progressive heart failure. A genetic variant of the ACE gene has been reported to be associated with increased risks of cardiovascular pathology. ACE INHIBITOR THERAPY: To date, studies of ACE inhibitor treatment in human patients have not demonstrated any prevention of restenosis after angioplasty. However, recent clinical trials in postmyocardial infarction reported that ACE inhibitor therapy reduces recurrent myocardial infarction and prevents cardiac enlargement. Long-term prospective trials are currently being conducted to examine the effects of ACE inhibitor therapy on coronary ischemic events and coronary atherosclerosis, as evaluated by angiography or intravascular ultrasound, and the relationship between coronary events and ACE gene polymorphism.
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PMID:Cell biology and genetics of angiotensin in cardiovascular disease. 796 71

A collagen network, composed largely of type I and III fibrillar collagens, is found in the extracellular space of the myocardium. This network has multiple functions which includes a preservation of tissue architecture and chamber geometry. Given its tensile strength, collagen is a major determinant of tissue stiffness. Its disproportionate accumulation, in the form of either a reactive or a reparative fibrosis, further increases stiffness. A degradation of collagen tethers, on the other hand, is an anatomic requisite for a distortion in tissue architecture and a reduction in stiffness that can lead to chamber dilatation, wall thinning, and even rupture of the myocardium. Collagen turnover in the myocardium is dynamic. When synthesis exceeds degradation, an adverse accumulation of collagen appears to distort tissue structure. This is true for either the hypertrophied and/or nonhypertrophied ventricle. Factors that contribute to the appearance of myocardial fibrosis are largely different from those that promote cardiac myocyte growth. Included amongst these fibrogenic factors are effector hormones of the reinin-angiotensin-aldosterone system (RAAS). Studies conducted both in intact animals (relative to dietary sodium intake) and in cultured adult cardiac fibroblasts have pointed toward the association between collagen accumulation and chronic elevations in circulating angiotensin II and aldosterone. A tissue hormonal system involving angiotensin II, endothelins and bradykinin, may likewise regulate fibrogenesis. In this regard, angiotensin converting enzyme is found in connective tissue of the normal heart, including the matrix of heart valves and the adventitia of the intramural coronary arteries, and fibrous tissue that forms following infarction or with chronic RAAS activation. The importance of ACE in the regulation of local angiotensin II and bradykinin levels and their contribution to collagen turnover is a fruitful area of research with important clinical implications. The myocardium also contains a proteolytic system, including collagenase. The characteristics and regulation of matrix metalloproteinases and their tissue inhibitors in various cardiovascular disease states requires further investigation.
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PMID:Collagen network of the myocardium: function, structural remodeling and regulatory mechanisms. 802 11

First, we had the discussion 'Are all ACE inhibitors equal?', and the debate was really in relation to heart failure. I came away with the impression that although there might be variations with renal function, hypotension and so on, most of you felt that it was ACE inhibition that was of primary importance, and that it was therefore permissible to extrapolate from one study to another. The recently published AIRE study of post-infarct patients used ramipril, with a change in mortality that gives credence to the idea that it's not just captopril, not just enalapril, but is likely to be a class effect of ACE inhibitors. I think that's the feeling I got from you. Do ACE inhibitors prolong life? I think Professor Weich made a very simple and a very good point, because it allowed us a general extrapolation. The simple point is: the sicker the patient, certainly with heart failure, the more the benefit of the ACE inhibitor. It's like the idea that in elderly hypertensives, or the diabetic hypertensive, the greater the risk factor the greater the benefit. The more we want to treat prophylactically, whether it's micro-albuminuria, or transient hypertension, or minimal left ventricular dysfunction, the longer we will have to treat, and the more patients we will have to treat to get objective evidence of any differences. Professor Oosthuizen suggested that we should also be thinking of renal impairment, potential renal impairment with cardiovascular disease in diabetes as another valid end-point.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The Grande Roche ACE debate. 804 78

A variety of lifestyle modification and drug therapies can be used to treat hypertension. Hypertension awareness, as well as drug treatment, and control rates have improved progressively in the United States during the last three decades. The extent to which lifestyle modification interventions are being utilized to treat hypertension is uncertain. There has been a progressive shift from antihypertensive drug therapy with diuretics and beta blockers toward treatment with newer and more expensive agents such as calcium channel blockers and angiotensin converting enzyme inhibitors. The newer agents are well tolerated and effective in lowering blood pressure but their efficacy in preventing cardiovascular disease complications is less well documented. In order to reduce the burden of blood pressure-related cardiovascular disease in the general population, treatment of hypertension must be complemented by a parallel strategy to prevent hypertension.
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PMID:Hypertension management in populations. 826 81

Hypertension is the commonest cardiovascular disease in Africans occurring in more than 15% of the adult population in some studies. It occurs in the lower as much as in the higher socio-economic groups. Recent studies have confirmed earlier findings that essential hypertension in Africans is characterised by volume loading, low plasma renin activity, high salt taste threshold, high urinary sodium and low potassium excretion and high plasma aldosterone. The commonest complication of hypertension in Africans is congestive cardiac failure followed by cerebrovascular accidents. Coronary heart disease is rare. Even in the absence of overt heart failure and compounding factors like obesity, alcoholism, cigarette smoking, diabetes mellitus and myocarditis, evidence of abnormal left ventricular morphology and function is often present in newly diagnosed patients with moderate or severe hypertension. Response to monotherapy with beta-blockers or ACE inhibitors is usually poor but is good with thiazide diuretics or calcium channel blockers. The diuretics are an essential component of a two or three drug regime containing other classes of antihypertensive drugs. Cost of drugs is the most important determinant of compliance with drug treatment and consequently the likelihood of progression of the diseases to more severe forms in long term follow-up.
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PMID:Hypertension in Africa and effectiveness of its management with various classes of antihypertensive drugs and in different socio-economic and cultural environments. 826 3

Hyperinsulinemia is very much in the spotlight. Debate rages as to its significance and role in the etiology not only of NIDDM, but also other morphological and metabolic risk factors for atherosclerotic cardiovascular disease, including upper-body obesity, dyslipidemia, hypertension, and hyperuricemia. Epidemiological data support a key role for hyperinsulinemia in these disorders but it is far from conclusive except for the fact that hyperinsulinemia and insulin resistance may be present many years before the onset of impaired glucose tolerance and NIDDM, and clearly play a role in their etiology. The thrifty genotype hypothesis provides a plausible basis for a better understanding of how hyperinsulinemia and insulin resistance could lead to glucose intolerance and atherosclerotic cardiovascular disease, but the detailed biochemical mechanisms remain elusive. A role for increased sympathetic nervous system activity, resulting from hypothalamic stimulation as a primary event causing hyperinsulinemia, cannot be excluded as a cause of hyperinsulinemia. The current focus on hyperinsulinemia also has resulted in closer examination of the therapy of diabetes and hypertension, emphasizing the need to avoid hyperinsulinemia in both IDDM and NIDDM individuals because of the putative risk of atherosclerotic cardiovascular disease and hypertension. There is still a paucity of epidemiological data to support a role for hyperinsulinemia in the etiology of hypertension. However, clinical practice already is being influenced by the fact that ACE inhibitors have been shown to reduce insulin resistance in clinical research studies. The research reviewed here, particularly that relating to hyperinsulinemia, insulin resistance, and cardiovascular disease risk factors, has opened new vistas for the treatment and prevention of NIDDM and atherosclerotic cardiovascular disease. Appropriate exercise clearly is associated with improved insulin sensitivity, modification of CVD risk factors, and lower prevalence of NIDDM. Upper-body obesity, the latest culprit in the field, can also be reduced by exercise. Hyperinsulinemia and insulin resistance can be detected in children, adolescents, and young adults. NIDDM can be prevented, but clearly, intervention needs to commence in childhood, and intensive risk factor intervention in subjects with NIDDM can reduce the risk of atherosclerotic cardiovascular disease. It seems paradoxical that prevention of NIDDM and atherosclerotic cardiovascular disease are now possible even though the biochemical and molecular basis of these disorders is not fully understood.
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PMID:Hyperinsulinemia--how innocent a bystander? 829 79

Non-insulin-dependent or type 2 diabetes is a heterogeneous disorder, characterized by defects in insulin secretion as well as in insulin action; these defects are worsened by the developing hyperglycaemia. Diabetes is an independent risk factor for the development of cardiovascular disease. In addition to hypertension, which is encountered in almost 50% of patients, lipid abnormalities, comprising elevations of both LDL-cholesterol and VLDL-triglycerides, as well as decreases in the levels of HDL-cholesterol, contribute to the high prevalence of vascular disease. Elevated levels of serum lipoprotein(a) may add to this increased risk. Considering the apparent clustering of risk factors such as poor metabolic control, obesity, hypertension and dyslipidaemia, the attainment of optimal blood glucose control forms only one of the aims of treatment to prevent the neurological and vascular complications, which severely affect the quality of life. Dietary advice comprises the adoption of healthy eating habits and reducing the intake of refined sugars and saturated fat. The long-term metabolic effects of intensive dietary therapy, however, have been disappointing. This necessitates early pharmacological treatment in a considerable number of patients. With mild hyperglycaemia, the metabolic effects of sulphonylurea and insulin treatment were comparable, but insulin is superior to sulphonylurea in patients who are more hyperglycaemic (fasting blood glucose > 11 mmol/l). In addition to its effects on blood glucose control, insulin therapy favourably affects dyslipidaemia. Treatment can be safely instituted on an outpatient basis, and hypoglycaemic side-effects are infrequent. Combination therapy of insulin and sulphonylurea results in similar metabolic improvement when compared with insulin treatment alone, but with a lower dose of insulin and the need for only one injection in two-thirds of patients. Drugs such as ACE inhibitors, which have no metabolic side-effects, have become the therapy of choice when treating hypertension in diabetic patients.
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PMID:Type 2 diabetes mellitus. Aspects of complications and treatment. 830 99


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