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)

Myocardial hypertrophy and extended cardiac fibrosis are independent risk factors for congestive heart failure and sudden cardiac death. Before age 50, men are at greater risk for cardiovascular disease than age-matched women. In the current studies, we found that cardiac hypertrophy and fibrosis were significantly more pronounced in males compared with females of guanylyl cyclase-A knockout (GC-A KO) mice at 16 wk of age. These gender-related differences were not seen in wild-type mice. In the further studies, either castration (at 10 wk of age) or flutamide, an androgen receptor antagonist, markedly attenuated cardiac hypertrophy and fibrosis in male GC-A KO mice without blood pressure change. In contrast, ovariectomy (at 10 wk of age) had little effect. Also, chronic testosterone infusion increased cardiac mass and fibrosis in ovariectomized GC-A mice. None of the treatments affected cardiac mass or the extent of fibrosis in wild-type mice. Overexpression of mRNAs encoding atrial natriuretic peptide, brain natriuretic peptide, collagens I and III, TGF-beta1, TGF-beta3, angiotensinogen, and angiotensin converting enzyme in the ventricles of male GC-A KO mice was substantially decreased by castration. The gender differences were virtually abolished by targeted deletion of the angiotensin II type 1A receptor gene (AT1A). Neither castration nor testosterone administration induced any change in the cardiac phenotypes of double-KO mice for GC-A and AT1A. Thus, we suggest that androgens contribute to gender-related differences in cardiac hypertrophy and fibrosis by a mechanism involving AT1A receptors and GC-A.
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PMID:Androgen contributes to gender-related cardiac hypertrophy and fibrosis in mice lacking the gene encoding guanylyl cyclase-A. 1459 59

This article contains a series of reports on recent research developments in the field of heart failure. Reports of key presentations made at the European Society of Cardiology meeting, held in Vienna, Austria, between 30 August and 3 September 2003 are reported. In the CHARM study, candesartan reduced cardiovascular deaths and hospital admissions for heart failure, both in patients who were already taking an ACE-inhibitor and in those who were ACE intolerant. However, results in patients with preserved left ventricular function were less conclusive. The BASEL study supports the use of B-type natriuretic peptide testing to confirm the diagnosis of heart failure in patients presenting with acute dyspnoea. In EUROPA, the largest ever study of secondary prevention of coronary artery disease, long-term treatment with perindopril reduced the incidence of cardiovascular death, myocardial infarction (MI) and cardiac arrest. The ESTEEM study showed that the oral thrombin inhibitor ximelagatran plus aspirin was more effective than aspirin alone in the prophylaxis of major cardiovascular events following MI.
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PMID:Clinical trials update from the European Society of Cardiology: CHARM, BASEL, EUROPA and ESTEEM. 1460 10

The human cardiovascular system is regulated by haemodynamic, neurohumoral and structural mechanisms. The endothelium and the neurohumoral system play a key role in modulating both vascular tone and structure by producing vasoactive substances, and in the modulation of blood cell adhesion. Although the neurohormonal systems are essential in vascular homeostasis, they become maladaptive in conditions such as hypertension, coronary disease and heart failure. The clinical success of blocking the renin-angiotensin system by angiotensin converting enzyme (ACE)-inhibitors and the sympathetic nerve system by beta-blockers demonstrates the importance of neurohumoral blockade. The inadequate effect of angiotensin converting enzyme (ACE) or neutral endopeptidase (NEP) inhibitor monotherapy seen in some patients treated for hypertension or congestive heart failure, and the promising effect seen after their combination, led to the development of drugs that simultaneously inhibit both enzyme systems. Neutral endopeptidase, like ACE, is an endothelial cell surface zinc metallopeptidase with similar structure and catalytic site to ACE. NEP is the major enzymatic pathway for degradation of natriuretic peptides. The natriuretic peptide system can be viewed as the endogenous inhibitor of the renin angiotensin system. The dual metalloprotease inhibitors of ACE and NEP, called vasopeptidase inhibitors therefore represent a new and attractive therapeutic strategy for the treatment of cardiovascular disease. The ability to add incremental benefit over already proven therapy, with an acceptable side-effect profile however, is questionable in this new class of agents.
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PMID:Vasopeptidase inhibitors: will they have a role in clinical practice? 1467 37

Sympathetic nerve system is activated as a compensatory mechanism in heart failure. However, excessive activation of sympathetic nerve system deteriorates disease state. Sympathetic nerve system can be suppressed with N-type Ca2+ channel blocker. An antihypertensive drug, cilnidipine, is a dual L/N-type Ca2+ channel blocker. We studies usefulness of cilnidipine in treating with chronic heart failure with 123I-MIBG myocardial scintigraphy. We enrolled 24 patients with stable chronic heart failure. Twelve patients were treated with ACE-inhibitors, diuretics and cardiotonics (control group), and the other 12 patients were treated with ACE-inhibitors, diuretics, cardiotonics and cilnidipine (cilnidipine group). We examined blood pressure, heart rate, norepinephrine level, brain natriuretic peptide (BNP) level, cardiothoracic ratio on chest X-ray, ejection fraction of left ventricle on two-dimensional echocardiography, count rate of heart to mediastinum (H/M) and washout rate (WOR) on 123I-MIBG myocardial scintigraphy before and six months after medication. Symptom was improved in 8 patients in the control group and 10 patients in the cilnidipine group after medication. And another parameters were also improved in the both groups after medication. However the degree of change in blood pressure (mmHg) was 21.2 +/- 8.0 in the cilnidipine group and 10.8 +/- 9.1 in the control group, that in heart rate (/min) was 24.1 +/- 6.8 and 16.2 +/- 11.0, that in BNP level (pg/ml) was 65.2 +/- 12.0 and 42.8 +/- 11.1, that in H/M was 0.30 +/- 0.08 and 0.19 +/- 0.09, that in WOR was 19.4 +/- 5.6 and 12.2 +/- 7.0, respectively. And the degree of these changes were larger in the cilnidipine group (p < 0.05). These findings suggested that cilnidipine, a dual L/N-type Ca2+ channel blocker, might be useful in treating with chronic heart failure.
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PMID:[Clinical usefulness of a dual L/N-type Ca2+ channel blocker, cilnidipine, in patients with chronic heart failure: assessment with 123I-MIBG myocardial scintigraphy]. 1473 6

A young patient presented with a cardiomegaly of unknown origin. The cardiologic examination revealed a severe eccentric left ventricular hypertrophy and a dilatation of the other heart cavities as well as a strongly impaired global systolic function. The patient was treated with an ACE inhibitor, a diuretic and with a beta-blocking agent. The dosages of which were adapted accordingly to the plasma concentration of N-terminal-pro-brain-natriuretic peptide (NT-proBNP). After five months of treatment, a decrease of the NT-proBNP level to nearly normal values along with a significant reduction of the heart dimensions and a substantial improvement of left ventricular function were found.
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PMID:[Severe heart failure: treatment optimisation and monitoring using plasma NT-proBNP levels--an useful tool in clinical practice]. 1507 35

Diabetes substantially increases the risk of heart failure both in men and women, being included in the Stage A classification of heart failure by the American Societies of Cardiology. The main etiological factors contributing to heart failure in diabetes are coronary artery disease, systemic hypertension and diabetic cardiomyopathy, the latter being invoked in case of heart failure where the first two factors are missing. Renal insufficiency and obesity may also play a role. The diagnosis will follow the same steps as in non-diabetic subjects: careful and periodic assessment for signs and symptoms of heart failure in all diabetic patients, echocardiography to assess the systolic and diastolic function of the left ventricle, and B-type natriuretic peptide level (as a marker of left ventricular dysfunction). The therapeutic approach will include non-pharmacological measures and pharmacological treatment. Patients with diabetes and heart failure benefit of the same drugs as non-diabetic subjects, including beta-blockers, which should not be avoided in patients with diabetes. The antihyperglycemic agents that should not be used in patients with heart failure are biguanides and thiazolidindiones (pioglitazone can be used in NYHA I and II classes). Approaches that were proven to reduce the risk of heart failure in diabetes are blood pressure and lipid control, treatment with ACE inhibitors in patients with diabetes and other cardiovascular risk factors and improvement of the glycemic control.
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PMID:Heart failure and diabetes. 1552 17

The present study was undertaken to examine the effects of a calcium channel blocker, azelnidipine (1 mg/kg/day), an angiotensin converting enzyme (ACE) inhibitor, temocapril (10 mg/kg/day), an angiotensin II type 1 (AT1) receptor blocker (ARB), olmesartan (5 mg/kg/day), and their combination on Dahl salt-sensitive rats (DS rats) developing heart failure with preserved systolic function. DS rats were fed a high-salt diet (8% NaCl) from 7 weeks of age and progressively developed hypertension. Although monotherapy with azelnidipine lowered the blood pressure of DS rats to a greater extent than monotherapy with temocapril or olmesartan, the three drugs had similar effects on cardiac hypertrophy, cardiac fibrosis, the expressions of brain natriuretic peptide, transforming growth factor-beta1, collagen I, collagen III and monocyte chemoattractant protein-1 mRNA (as estimated by Northern blot analysis), and cardiac diastolic dysfunction (as estimated by echocardiography). These results show that ACE and AT1 receptor, as well as hypertension, are involved in the development of heart failure with preserved systolic function in DS rats. The combination of azelnidipine with olmesartan or temocapril produced no additive hypotensive effect in DS rats and no additive effect on cardiac hypertrophy or gene expressions. However, the combination therapy prolonged the survival rate of DS rats more than azelnidipine (p <0.01) or temocapril alone (p <0.05), and this additive beneficial effect by the combination therapy was associated with a greater reduction of cardiac fibrosis, urinary albumin excretion and serum creatinine. Our results thus showed that the combination of a calcium channel blocker with an ARB or an ACE inhibitor had additive preventive effects on a rat model of hypertensive heart failure with preserved systolic function. Thus, combination therapy with these agents seems to be a useful therapeutic strategy for the prevention of hypertensive heart failure.
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PMID:Additive beneficial effects of the combination of a calcium channel blocker and an angiotensin blocker on a hypertensive rat-heart failure model. 1578 13

Congestive heart failure (CHF) is a life-threatening cardiovascular disease that is increasing in prevalence. It is a common cause of death and is accompanied by high direct and indirect costs for treatment. The current situation faced by patients and the medical community with regard to this ailment is one of high mortality, repeated hospitalizations, and combination therapies. The various classes of pharmacological agents that are currently used for patients suffering from CHF include angiotensin converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), aldosterone antagonists, beta-blockers, calcium channel blockers (CCBs), digitalis drugs, diuretics, inotropic agents, nitrates, and vasodilators. While these agents are all important therapeutic tools in the treatment of CHF, the prognosis for patients with CHF remains poor. Thus improvement of the current pharmacological armamentarium is greatly needed. An endogenous peptide, B-type natriuretic peptide (BNP), has been increasingly utilized in the setting of acute CHF since its approval in 2001. This peptide, or a derivative thereof, has great potential for the treatment of patients at various stages in the progression of heart failure. This review provides an overview of current pharmacological strategies in CHF and addresses potential future developments in the use of BNP for the treatment of CHF.
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PMID:Congestive heart failure: pharmacological agents and the potential of B-type natriuretic Peptide. 1597 94

Aside from the important role of brain natriuretic peptide (BNP) in diagnosis, and differential diagnosis of heart failure, this biological peptide has proved to be an independent surrogate marker of rehospitalization and death of the fatal disease. Several randomized clinical trials demonstrated that drugs such as beta blocker, angiotensin converting enzyme inhibitor, spironolactone and amiodarone have beneficial effects in decreasing circulating BNP level during the management of chronic heart failure. The optimization of clinical decision-making appeals for a representative surrogate marker for heart failure prognosis. The serial point-of-care assessments of BNP concentration provide a therapeutic goal of clinical multi-therapy and an objective guidance for optimal treatment of heart failure. Nevertheless new questions and problems in this area remain to be clarified. On the basis of current research advances, this article gives an overview of BNP peptide and its property and role in the management of heart failure.
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PMID:Brain natriuretic peptide and optimal management of heart failure. 1613 Jan 89

The aim of the present study was to investigate how early the onset of ischaemia-induced changes in gene expression is in remote myocardium, and whether these changes would be different for left and right ventricles. Wistar rats (n=27) were randomly assigned to left coronary artery (LCA) ligation for 30 or 120 min and sham groups. Evans Blue infusion revealed antero-apical left ventricle (LV) and left intraventricular (IV) septal ischaemia (35.5+/-0.6% of LV mass). LCA ligation induced transient LV systolic dysfunction and sustained biventricular slowing of relaxation. Regarding mRNA levels, type B natriuretic peptide (BNP) was upregulated in the LV at 30 (+370+/-191%) and 120 min (+221+/-112%), whilst in the right ventricle (RV) this was only significant at 120 min (+128+/-39%). Hipoxia-inducible factor 1alpha and interleukin 6 overexpression positively correlated with BNP. Inducible NO synthase upregulation was present in both ventricles at 120 min (LV, +327+/-195%; RV, +311+/-122%), but only in the RV at 30 min (+256+/-88%). Insulin-like growth factor 1 increased in both ventricles at 30 (RV, +59+/-18%; LV, +567+/-192%) and 120 min (RV, +69+/-33%; LV, +120+/-24%). Prepro-endothelin-1 was upregulated in the RV at 120 min (+77+/-25%). Ca2+-handling proteins were selectively changed in the LV at 120 min (sarcoplasmic reticulum Ca2+ ATPase, 53+/-7%; phospholamban, +31+/-4%; Na+-Ca2+ exchanger, 31+/-6%), while Na+-H+ exchanger was altered only in the RV (-79+/-5%, 30 min; +155+/-70%, 120 min). Tumour necrosis factor-alpha and angiotensin converting enzyme were not significantly altered. A very rapid modulation of remote myocardium gene expression takes place during myocardial ischaemia, involving not only the LV but also the RV. These changes are different in the two ventricles and in the same direction as those observed in heart failure.
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PMID:Remote myocardium gene expression after 30 and 120 min of ischaemia in the rat. 1640 72


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