Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018801 (heart failure)
 72,216 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The concept of cardiac remodeling implies a complex mixture of myocardial ischemia, and increased wall stress that results in molecular, cellular and interstitial changes in the heart. Clinically, cardiac remodeling is manifested as a change in size, shape and function of the heart. Morphologically the key feature of remodeling is myocyte hypertrophy, myocyte loss from necrosis or apoptosis, as well as interstitial cell growth especially fibroblast proliferation leading to myocardial fibrosis. Cardiac remodeling is influenced by hemodynamic load, neurohumoral activation, and other factors that can further affect the remodeling process. Despite advances in the management of heart failure, morbidity and mortality still present major health care issues in these patients. Statins (HMG Coenzyme A reductase inhibitors) play a key role in the management of ischemic heart disease. Recent studies indicate that statins may modulate cardiac remodeling by affecting signals that cause fibroblast growth, and myocyte hypertrophy and loss. In this paper we review the mechanisms of cardiac remodeling and the mechanisms of potential beneficial effects of statins on cardiac remodeling.
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PMID:Modulation of cardiovascular remodeling with statins: fact or fiction? 1563 84

Treatment with monocrotaline causes pulmonary hypertension in rats. This results in severe pressure overload-induced hypertrophy of the right ventricles, whilst the normally loaded left ventricles do not hypertrophy. Both ventricles are affected by enhanced neuroendocrine stimulation in this model. We analyzed in this model load-induced and catecholamine-induced changes of right and left ventricular proteome by two-dimensional gel electrophoresis, tryptic in-gel digest, and matrix-assisted laser desorption/ionization-time of flight mass spectrometry. All analyzed animals showed right ventricular hypertrophy without signs of heart failure. Changes of 27 proteins in the right and 21 proteins in the left ventricular myocardium were found. Given the hemodynamic features of this animal model, proteome changes restricted to the right ventricle are caused by pressure overload. We describe for the first time a potentially novel pathway (BRAP2/BRCA1) that is involved in myocardial hypertrophy. Furthermore, we demonstrate that increased afterload-induced hypertrophy leads to striking changes in the energy metabolism with down-regulation of pyruvate dehydrogenase (subunit beta E1), isocitrate dehydrogenase, succinyl coenzyme A ligase, NADH dehydrogenase, ubiquinol-cytochrome C reductase, and propionyl coenzyme A carboxylase. These changes go in parallel with alterations of the thin filament proteome (troponin T, tropomyosin), probably associated with Ca(2+) sensitization of the myofilaments. In contrast, neurohumoral stimulation of the left ventricle increases the abundance of proteins relevant for energy metabolism. This study represents the first in-depth analysis of global proteome alterations in a controlled animal model of pressure overload-induced myocardial hypertrophy.
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PMID:Pressure overload and neurohumoral activation differentially affect the myocardial proteome. 1573 35

Statins, also known as 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors, consistently reduce cardiovascular risk. It has recently emerged that cholesterol reduction is not their only mode of action, with current research largely focused on the pleiotropic effects of statins. These include the improvement of endothelial dysfunction, their anti-inflammatory properties, and the mobilization of bone marrow-derived endothelial progenitor cells. All these effects are potentially beneficial in chronic heart failure (CHF), although prospective trials are needed to confirm this. However, cholesterol reduction by statins per se may prove detrimental in patients with CHF, as cholesterol seems to be able to inactivate endotoxin as a stimulus for proinflammatory cytokine production. It is therefore tempting to speculate that low doses of statins still confer pleiotropic effects without lowering plasma cholesterol levels.
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PMID:Statins: a treatment option for chronic heart failure? 1577 4

3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, or statins, reduce morbidity and mortality in patients with coronary artery disease (CAD). Because CAD is the major cause of heart failure (HF) in developed countries, prevention of CAD may result in reduced HF. Evidence from randomized trials on lipid reduction (Cholesterol and Recurrent Events and the Scandinavian Simvastatin Survival Study) has shown statins to decrease progression to HF. Recently, many beneficial effects of statins have been demonstrated beyond cholesterol lowering. These agents improve endothelial function, exhibit anti-inflammatory properties, and prevent cardiac hypertrophy. Experimental studies have shown attenuation of left ventricular remodeling after myocardial infarction, possibly through reduced oxidative stress. However, no clinical evidence exists to support an effect on ventricular remodeling. Small, short-lasting clinical studies have also suggested that statin therapy might be associated with improved survival in ischemic and nonischemic HF.
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PMID:Do statins prevent heart failure in patients after myocardial infarction? 1603 39

Oxidative stress is one of the new and most intriguing pathogenetic hypotheses of heart failure; it involves various mechanisms such as endothelial dysfunction, mechano-energetic uncoupling and apoptosis. Xanthine oxidase, a key enzyme in purine catabolism, is overexpressed in patients with heart failure, and it is also an important source of oxidizing activity molecules (free radicals, superoxide anion, oxygen peroxide, etc...). Allopurinol competitively inhibits the action of xanthine oxidase and effectively counters oxidative stress. It could thus prove useful in the treatment of heart failure: in fact it is the only drug that has been proven able to lower O2 consumption of dysfunctioning myocardium. The Authors briefly review the xanthine oxido-reductase enzyme system and in particular analyse the latest evidence reported in the literature on allopurinol in the treatment of heart failure.
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PMID:Heart failure, oxidative stress and allopurinol. 1612 62

Hydroxymethylglutaryl-coenzyme A reductase inhibitors (statins) are a group of cholesterol lowering agents that have become the largest selling drugs in the world. They are of proven clinical benefit in coronary heart disease, at least in those patients who do not have overt chronic heart failure (CHF). Co-administration of statins with angiotensin II receptor blockers (ARBs) is most common, since there is strong synergy between hypertension and hypercholesterolemia in terms of risk factors for the development of cardiovascular diseases. In present paper, we describe the in vitro availability of atorvastatin, a potent HMG-CoA reductase inhibitor, in presence of losartan potassium, which is a non-peptide angiotensin II receptor antagonist. These studies were carried out at 37, 48 and 60 degrees C in different pH environments simulating human body compartments. It was observed that in pH 1, 7.4 and 9 the availability of atorvastatin was very high while losartan was not at all available. However in pH 4 these effects were reversed and atorvastatin was not available at all. At 48 degrees C the availability of atorvastatin was high and that of losartan was depressed at pH 9, whereas the later was not available at pH 1, 4 and 7.4 at all. Likewise at 60 degrees C, the availability of atorvastatin at pH 7.4 and 9 was high, whereas the charge-transfer complex formed between the two drugs was broken at pH 1 at this temperature and the entire drug was available. On the other hand the availability of losartan at pH 4 and 9 was high while it was not available at pH 1 and 7.4. The availability of atorvastatin was maximum in simulated gastric juice as compared to buffer of pH 7.4 and 9. This high availability of one drug in presence of other is attributed to the formation of a charge-transfer complex, which was stable at elevated temperatures, except at 60 degrees C in pH 1.
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PMID:In vitro availability of atorvastatin in presence of losartan. 1675 Nov 25

The thioredoxin (TRX) system (TRX, TRX reductase, and NADPH) is a ubiquitous thiol oxidoreductase system that regulates cellular reduction/oxidation (redox) status. The impairment of cell redox state alters multiple cell pathways, which may contribute to the pathogenesis of cardiovascular disorders including hypertension, atherosclerosis, and heart failure. In this manuscript, we review the essential roles that TRX plays by limiting oxidative stress directly via antioxidant effects and indirectly by protein-protein interactions with key signaling molecules such as thioredoxin interacting protein (TXNIP). TRX and its endogenous regulators may represent important future targets to develop clinical therapies for diseases associated with oxidative stress.
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PMID:Thioredoxin in the cardiovascular system. 1702 8

Statins are drugs that inhibit 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase, thereby blocking the synthesis of cholesterol. Since being discovered in Japan in the mid 1970s, statins have been widely used to lower low-density lipoprotein cholesterol. However, analysis of cardiovascular research has revealed other important effects beyond changes in lipid parameters, referred to as pleiotropic effects. This paper focuses on the effects of statins as anti-ischemic agents with improvement in endothelial function, along with studies on valvular aortic stenosis, atrial fibrillation, heart failure, peripheral arterial disease, and cancer. As the evolution of statin research continues, there appear to be new potential benefits from statins to be found in many facets of cardiovascular disease.
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PMID:Statin therapy in cardiovascular diseases other than atherosclerosis. 1722 87

HMG-CoA (3-hydroxy-3-methylglutaryl-CoA) reductase inhibitors (statins) are well-established therapies in the prevention and treatment of cardiovascular disease, reducing all-cause mortality and cardiovascular events in many disease states. Studies have also suggested that statins given to patients after myocardial infarction improve event-free survival even in short time frames; however, evidence for the benefit of statins in established HF (heart failure) has not been demonstrated with the same rigour of a randomized clinical trial setting. In fact, clinical data examining the effect of statins in HF have been limited by the retrospective or observational nature of these analyses, examination of incompletely validated surrogate end points, small prospective studies in subgroups of HF subjects, and non-uniform doses and different statins being used. In this review, we examine the evidence for the effect of statins on mortality in HF, taking into account theoretical arguments, appropriateness of surrogate markers, animal data and analysis of the predominantly retrospective clinical data that is currently available.
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PMID:Statins and clinical outcomes in heart failure. 1760 May 28

Several evidences point for beneficial effects of growth hormone (GH) in heart failure (HF). Taking into account that HF is related with changes in myocardial oxidative stress and in energy generation from metabolic pathways, it is important to clarify whether GH increase or decrease myocardial oxidative stress and what is its effect on energetic metabolism in HF condition. Thus, this study investigated the effects of two different doses of GH on energetic metabolism and oxidative stress in myocardium of rats with HF. Male Wistar rats (n=25) were submitted to aortic stenosis (AS). The HF was evidenced by tachypnea and echocardiographic criteria around 28 weeks of AS. The rats were then randomly divided into three groups: (HF) with HF, treated with saline (0.9% NaCl); (HF-GH1), treated with 1 mk/kg/day recombinant human growth hormone (rhGH), and (HF-GH2) treated with 2 mg/kg/day rhGH. GH was injected, subcutaneously, daily for 2 weeks. A control group (sham; n=12), with the same age of the others rats was evaluated to confirm data for AS. HF had lower IGF-I (insulin-like growth factor-I) than sham-operated rats, and both GH treatments normalized IGF-I level. HF-GH1 animals had lower lipid hydroperoxide (LH), LH/total antioxidant substances (TAS) and glutathione-reductase than HF. Glutathione peroxidase (GSH-Px), hydroxyacyl coenzyme-A dehydrogenase, lactate dehydrogenase(LDH) were higher in HF-GH1 than in HF. HF-GH2 compared with HF, had increased LH/TAS ratio, as well as decreased oxidized glutathione and LDH activity. Comparing the two GH doses, GSH-Px, superoxide dismutase and LDH were lower in HF-GH2 than in HF-GH1. In conclusion, GH effects were dose-dependent and both tested doses did not aggravate the heart dysfunction. The higher GH dose, 2 mg/kg exerted detrimental effects related to energy metabolism and oxidative stress. The lower dose, 1mg/kg GH exerted beneficial effects enhancing antioxidant defences, reducing oxidative stress and improving energy generation in myocardium of rats with heart failure.
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PMID:Growth hormone and heart failure: oxidative stress and energetic metabolism in rats. 1819


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