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

---

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

These two issues of Progress in Pediatric Cardiology comprehensively illustrate the wealth of currently available information on the pathophysiology of heart failure, age-related myocardial responsiveness, energy metabolism, cardiopulmonary interactions, the pressure-volume relationship, the systemic inflammatory response, the management of heart failure, pediatric pharmacology, the use of heart failure therapies including digoxin, ACE inhibitors, beta-adrenergic blockers, inotropic agents, diuretics, vasodilators, calcium sensitizers, angiotensin and aldosterone receptor blockers, growth hormone, and future gene therapy. The etiology and course of ventricular dysfunction in children is poorly characterized. Furthermore, many changing developmental properties of the pediatric myocardium and differences in the etiologies of ventricular dysfunction in children compared with adults are illustrated in these articles, invalidating the concept that children can safely be considered small adults for the purpose of understanding heart failure pathophysiology and treatment. However, these articles reveal that strikingly little research in children with ventricular dysfunction exists in terms of well-designed large-scale studies of the epidemiology or multicenter controlled clinical therapeutic trials. A future research agenda is proposed to improve understanding etiologies, course and treatment of ventricular dysfunction in children that is based on organized and funded cooperative groups since no one pediatric cardiac center treats enough children with a particular etiology of ventricular dysfunction. In conclusion, significant understanding of basic mechanisms of pediatric ventricular dysfunction and effective therapies for adults with ventricular dysfunction exist. A multicenter pediatric cardiac ventricular dysfunction network would allow improved understanding of diseases and treatments, and result in evidence-based medicine for pediatric patients with ventricular dysfunction.
...
PMID:Ventricular dysfunction clinical research in infants, children and adolescents. 1111 43

Despite major advances many cardiovascular disorders remain poorly controlled. As a result the search for newer agents goes on. Anti-neurohormonal agents have been the most successful agents: beta-blockers, ACE inhibitors and angiotensin receptor blockers. To these we now add anti-aldosterone strategies with the phenomenal success of spironolactone in reducing mortality in severe heart failure. A more recent and more selective aldosterone receptor antagonist has been developed, eplerenone, and it shows considerable promise in managing and preventing the complications of hypertension. It may have a role both being anti-fibrotic and anti-neurohormonal in mild to moderate heart failure, in post-MI left ventricular dysfunction and in progressive renal disease. The EPHESUS trial which randomised patients with heart failure due to impaired left ventricular systolic function aims to randomise 6,200 patients to eplerenone or placebo on top of standard therapy and follow subjects until 1,012 deaths have occurred (approx. 2.5 years of follow up). This and other trials with the novel strategy of selective aldosterone antagonism are eagerly awaited. The beneficial effects established by the earliest anti-neurohormonal agents give us confidence that further benefits could be obtained by this intellectual strategy.
...
PMID:Exciting new drugs on the horizon - eplerenone, a selective aldosterone receptor antagonist (SARA). 1153 39

We analyzed the association between salt sensitivity in essential hypertension and 8 genetic polymorphisms in 6 genes of the renin-angiotensin aldosterone system. Seventy-one patients with essential hypertension were classified as salt sensitive or salt resistant by means of the 24-hour ambulatory blood pressure (BP) change to high salt intake. The polymorphisms evaluated correspond to the following genes: ACE (I/D), angiotensinogen (M235T), angiotensin II type 1 receptor (A1166C), 11beta-Hydroxysteroid dehydrogenase type 2 (11betaHSD2) (G534A), aldosterone synthase (C-344T and Intron 2 conversion), and the mineralocorticoid receptor (G3514C and A4582C); all were determined using standard polymerase chain reaction methods. Thirty-five patients (49%) were classified as salt sensitive. We analyzed the BP response to high salt intake among genotypes and found a significant association for ACE I/D and 11betaHSD2 G534A polymorphisms. Patients homozygous for the insertion allele of the ACE gene (II) had a significantly higher BP increase with high salt intake than did patients homozygous for the deletion allele (DD). Heterozygous patients (ID) exhibited an intermediate response. The prevalence of salt-sensitive hypertension was also significantly higher (P=0.003) in II (68%) and DI patients (59%) compared with DD hypertensives (19%). With respect to 11betaHSD2 G534A, patients with the GG genotype had a significantly higher systolic BP increase with high salt intake than did GA patients. In addition, plasma renin activity suppression in response to high salt was significantly greater in GA patients than in GG patients. The prevalence of salt-sensitive hypertension was 14.3% in GA patients and 50.8% in GG patients (P=0.067). In conclusion, the I allele of ACE I/D polymorphism is significantly associated to salt-sensitive hypertension. The BP response to high salt intake was different among genotypes of ACE I/D and 11betaHSD G534A, suggesting that these polymorphisms may be potentially useful genetic markers of salt sensitivity.
...
PMID:Molecular basis of salt sensitivity in human hypertension. Evaluation of renin-angiotensin-aldosterone system gene polymorphisms. 1171 24

The role of aldosterone in the pathophysiology of congestive heart failure (CHF) has long been recognized. The recent RALES (Randomized Aldactone Evaluation Study) trial demonstrated early reduction in morbidity and mortality using spironolactone, an aldosterone receptor antagonist, in combination with angiotensin converting enzyme (ACE) inhibitor and loop diuretic, in patients with heart failure. This effect of spironolactone highlighted the importance of understanding the contributions of the renin-angiotensin-aldosterone system (RAAS) in the progression of CHF, and increased interest in the use of aldosterone antagonists. While ACE inhibitors have had the largest impact on adverse events in CHF, numerous studies have shown that these drugs fail to completely suppress aldosterone. Blocking the effects of residual aldosterone has now been demonstrated to affect prognosis in these patients. This review will discuss the role of aldosterone in the pathophysiology of CHF, with an emphasis on both known and potential therapeutic benefits of aldosterone antagonism.
...
PMID:Aldosterone antagonists in congestive heart failure. 1218 62

ACC/AHA Guidelines for the Evaluation and Management of Chronic Heart Failure in the Adult are summarized in detail. According to statements of these Guidelines most patients with chronic heart failure as a rule should receive combination of representatives of 4 different drug classes - diuretic, angiotensin converting enzyme inhibitor, beta-adrenoblocker and usually digoxin. Special indications have been formulated for inclusion in complex therapy of aldosterone receptor blockers (first of all spironolactone), angiotensin1 receptor blockers and direct vasodilators (hydralazine, isosorbide dinitrate).
...
PMID:[Contemporary approaches to diagnosis and management of chronic heart failure (summary of the American College of Cardiology/American Heart Association Guidelines)]. 1249 35

Mineralocorticoid receptor (MR) antagonists have been used as potassium-sparing diuretics in hypertension. However, in addition to their diuretic and secondary blood pressure (BP)-lowering effects, there exists strong evidence from clinical and experimental studies that they prevent aldosterone-induced myocardial fibrosis independent of their effect on BP. Sustained elevation of aldosterone levels and increased sodium intake in animal models has been found to induce myocardial fibrosis. Fibrosis of the right ventricle, the atria, and the pulmonary artery supports the concept that these effects are BP independent, corroborated by the finding that spironolactone in a dosage not sufficient to lower BP prevents myocardial fibrosis. Patients suffering from primary hyperaldosteronism or Conn's adenoma show more myocardial fibrosis, as assessed by echocardiography, than essential hypertensive patients. Several mechanisms have been proposed to mediate the profibrotic effects of aldosterone, including the possibility of local aldosterone production in the heart, an increase of myocardial AT(1)-receptor density, and enhanced local angiotensin converting enzyme expression. Furthermore, aldosterone increases endothelin receptor expression, which also might cause myocardial fibrosis. Because of the pivotal importance of aldosterone binding to the MR, MR antagonists have emerged as attractive compounds that provide specific end organ protection beyond solely their antihypertensive effects.
...
PMID:Aldosterone-induced cardiac damage: focus on blood pressure independent effects. 1251 89

There is no evidence that loop diuretics improve ventricular remodeling in patients with heart failure. Aldosterone receptor antagonists, which have an effect on natriuresis and diuresis, especially in conjunction with an angiotensin converting enzyme-inhibitor, have been shown to improve ventricular remodeling in patients with left ventricular systolic dysfunction. The mechanisms for this beneficial effect and a reduction in death due to progressive heart failure seen in the randomized aldosterone evaluation study (RALES) is likely related to the effect of aldosterone receptor antagonism on myocardial collagen formation and ventricular hypertrophy. Further proof of this hypothesis should be forthcoming from the results of the Eplerenone Heart Failure Efficacy and Survival Study (EPHESUS) early in 2003 in which the aldosterone receptor antagonist eplerenone is being evaluated in patients with systolic left ventricular dysfunction post myocardial infarction.
...
PMID:Do diuretics and aldosterone receptor antagonists improve ventricular remodeling? 1255 63

Based upon the results of the RALES trial and accumulating evidence about the role of aldosterone and aldosterone receptor antagonism in various disease states, the authors anticipate that aldosterone receptor antagonists will become standard therapy, along with ACE inhibitors and beta-adrenergic receptor blocking agents, in patients with heart failure that is caused by systolic left ventricular dysfunction. Furthermore, the prospect of the use of these agents in other disease states that have implicated an activated rennin-angiotensin-aldosterone cascade, such as diastolic dysfunction, aging, and atherosclerosis, remains to be tested. Until further data from well-designed, prospective, randomized trials are available, the use of aldosterone receptor antagonists should be restricted to patients with severe or progressive heart failure caused by systolic left ventricular dysfunction in whom serum creatinine level is < or = 2.0 mg/dL and serum potassium levels are < 5.0 meq/L at baseline.
...
PMID:Aldosterone as a target in congestive heart failure. 1269 33

Although the role of the systemic renin-angiotensin-aldosterone system in the pathophysiology of heart failure is well-known for years, the impact of a local cardiac aldosterone system has been recognized recently. Aldosterone promotes cardiac hypertrophy and fibrosis in hypertension and heart failure and is involved in left ventricular remodeling after myocardial infarction. Plasma aldosterone levels in patients with heart failure are an indicator of a worse prognosis. Although ACE inhibitor therapy in these patients reduces plasma aldosterone levels, this effect is only transitory, a phenomenon referred to as "aldosterone escape". Even maximally recommended doses of ACE inhibitors do not completely prevent ACE-mediated formation of angiotensin II in chronic heart failure, and those patients with increased aldosterone levels during ACE inhibition have impaired exercise capacity. The RALES study has demonstrated convincingly that in patients with heart failure, addition of the mineralocorticoid receptor antagonist spironolactone (25 mg/d) to ACE inhibition markedly reduces mortality and prevents worsening heart failure. While reduction of excessive extracellular matrix turnover leading to decreased fibrosis appears to be the most important effect of spironolactone in heart failure, other mechanisms such as regression of hypertrophy, improvement of endothelial function, enhanced renal sodium excretion and antiarrhythmic actions may contribute. In RALES, low-dose spironolactone did not confer a substantial risk of hyperkalemia, however, with broader use of spironolactone in heart failure, cases of hyperkalemia associated with the use of this drug increase. Close control of serum potassium and creatinine and estimation of creatinine clearance are mandatory, especially in the presence of additional factors impairing renal function. The new and more selective aldosterone antagonist eplerenone which is devoid of some side effects of spironolactone, has been shown to be effective in hypertension and holds great promise as future therapeutic agent in patients with heart failure.
...
PMID:Aldosterone antagonism in addition to angiotensin-converting enzyme inhibitors in heart failure. 1278 71

An increased risk of thrombembolic events in congestive heart failure (CHF) has been attributed to a hypercoagulable state including vascular endothelial dysfunction and platelet activation. After experimental myocardial infarction, male Wistar rats were treated with placebo, the ACE inhibitor trandolapril, the selective aldosterone receptor antagonist eplerenone or the combination of both, for 10 weeks. Platelet-bound fibrinogen and surface-expressed P-selectin were not modulated in rats without CHF compared with sham-operated animals, but were significantly increased in CHF rats (LVEDP>15 mmHg). In CHF rats, ACE inhibition significantly reduced platelet P-selectin expression while bound fibrinogen was not modulated. Eplerenone reduced P-selectin expression to a comparable extent, while platelet-bound fibrinogen was normalised. Combination therapy with eplerenone and trandolapril completely abolished both the increased P-selectin expression as well as fibrinogen binding. Phosphorylation of platelet vasodilator-stimulated phosphoprotein (VASP) at both Ser(157) and Ser(239), which reflects the activity of platelet inhibitors including nitric oxide, was significantly reduced in platelets from placebo-treated CHF rats, and was completely normalised by combination treatment, but only marginally increased by either mono-therapy. The results show that platelet activation was evident only in CHF rats. Monotherapy with ACE inhibition or eplerenone partially reduced this increased platelet activation, which was completely rescued to basal levels by combination therapy. Increased nitric oxide bioavailability can only partially explain the reduced platelet activation by eplerenone and ACE inhibition.
...
PMID:Inhibition of platelet activation in congestive heart failure by aldosterone receptor antagonism and ACE inhibition. 1278 15


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>

---