Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038187 (starvation)
 24,951 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Progressive deterioration of the failing heart is now recognized to be a major cause of disability and death in patients with congestive heart failure. It appears that although the normal human heart functions for at least 90-100 years, overload-induced hypertrophy shortens the heart's life span to about 5 years. This accelerated deterioration of the failing heart can be viewed as a cardiomyopathy of overload in which chronic overloading causes changes in the myocardial cells that, while increasing cell mass, reduce their long-term viability. Although the pathogenesis of this putative cardiomyopathy remains poorly understood, chronic energy starvation and altered myocardial cell growth and composition appear to be contributing factors. Preferential expression of fetal isoforms of key muscle proteins, which accompanies accelerated growth of the overloaded heart, may contribute to this cardiomyopathy. The hypothesis that the cardiomyopathy of overload is due in part to a growth abnormality is supported by evidence that deterioration of the failing heart is slowed by the converting enzyme inhibitors, which may attenuate important effects of angiotensin II to stimulate cellular growth.
J Cardiovasc Pharmacol 1991
PMID:The cardiomyopathy of overload: a hypothesis. 172 47

The effect of disopyramide, a class Ia antiarrhythmic drug, on the serum glucose level was evaluated in 6 consecutive in-patients. A 19-hour starvation test was repeated with oral administration of sustained-release disopyramide (150 mg) 0 and 12 hours after starting the test. Serum glucose levels during the starvation test decreased with disopyramide administration from a mean value of 96.5 +/- 1.8 to 85.9 +/- 1.4 mg/dl (24 samples, p < 0.05). The average reduction of the serum glucose level by disopyramide in each patient was 9.7 +/- 2.2 mg/dl. The decrease in the serum glucose level was not related to the serum concentration of disopyramide or serum creatinine levels. The decrease in the serum glucose level was larger in older patients (r = 0.75) and in light patients under 45 kg. These results suggested that disopyramide reduced the fasting serum glucose levels even in normal ranges as a common side effect of the drug, and that not only the occurrence of severe hypoglycemia but also the decrease in glucose levels were influenced by multiple factors including age and body weight.
Cardiovasc Drugs Ther 1999 Jul
PMID:Disopyramide decreases the fasting serum glucose level in man. 1051 68

Cardiac energy metabolic shifts occur as a normal response to diverse physiologic and dietary conditions and as a component of the pathophysiologic processes which accompany cardiac hypertrophy, heart failure, and myocardial ischemia. The capacity to produce energy via the utilization of fats by the mammalian postnatal heart is controlled in part at the level of expression of nuclear genes encoding enzymes involved in mitochondrial fatty acid beta-oxidation (FAO). The principal transcriptional regulator of FAO enzyme genes is the peroxisome proliferator-activated receptor alpha (PPARalpha), a member of the ligand-activated nuclear receptor superfamily. Among the ligand activators of PPARalpha are long-chain fatty acids; therefore, increased uptake of fatty acid substrate into the cardiac myocyte induces a transcriptional response leading to increased expression of FAO enzymes. PPARalpha-mediated control of cardiac metabolic gene expression is activated during postnatal development, short-term starvation, and in response to exercise training. In contrast, certain pathophysiologic states, such as pressure overload-induced hypertrophy, result in deactivation of PPARalpha and subsequent dysregulation of FAO enzyme gene expression, which sets the stage for abnormalities in cardiac lipid homeostasis and energy production, some of which are influenced by gender. Thus, PPARalpha not only serves a critical role in normal cardiac metabolic homeostasis, but alterations in PPARalpha signaling likely contribute to the pathogenesis of a variety of disease states. PPARalpha as a ligand-activated transcription factor is a potential target for the development of new therapeutic strategies aimed at the prevention of pathologic cardiac remodeling.
Trends Cardiovasc Med 2000 Aug
PMID:PPAR signaling in the control of cardiac energy metabolism. 1128 1

It has been postulated that the failing heart suffers from chronic energy starvation, and that derangements in cardiac energy conversion are accessory to the progressive nature of this disease. The molecular mechanisms driving this 'metabolic remodelling' process and their significance for the development of cardiac failure are still open to discussion. Next to changes in mitochondrial function, the hypertrophied heart is characterized by a marked shift in substrate preference away from fatty acids towards glucose. It has been argued that the decline in fatty acid oxidation is not fully compensated for by a rise in glucose oxidation, thereby imposing an additional burden on overall ATP generating capacity. Several lines of evidence suggest that these metabolic adaptations are brought about, at least in part, by alterations in the rate of transcription of genes encoding for proteins involved in substrate transport and metabolism. Here, the principal metabolic changes are reviewed and the various molecular mechanisms that are likely to play a role are discussed. In addition, the potential significance of these changes for the aetiology of heart failure is evaluated.
Cardiovasc Res 2004 Feb 01
PMID:Metabolic remodelling of the failing heart: the cardiac burn-out syndrome? 1473 38

The Impact Of Nicorandil in Angina (IONA) randomized trial showed a significant reduction in coronary events, in patients with stable angina treated with a KATP channel opener, nicorandil. However, the impact of nicorandil on endothelial apoptosis remains to be examined. We tested the hypothesis that nicorandil has anti-apoptotic effects in endothelial cells (ECs). Apoptosis was induced by serum starvation in the culture media in human umbilical vein endothelial cells. We examined the effects of nicorandil on endothelial cell apoptosis. Cell viability after serum starvation was significantly higher in the nicorandil-treated group compared with the control group (81 +/- 8% vs. 63 +/- 3%, P < 0.01). Apoptosis, as detected by caspase 3 activation and Hoechst 33258 assay, induced by serum starvation was also effectively abrogated by the treatment of nicorandil (100 muM). The protective effects of nicorandil on endothelial survival were significantly inhibited by a specific mitochondrial KATP channel blocker, 5-Hydroxydecanoic acid. A mitochondrial permeability transition pore activator significantly abolished the anti-apoptotic effect of nicorandil in endothelial cells, indicating that the mechanism of protective effect of nicorandil is involved in the mitochondrial apoptotic pathway although it affects neither Bcl-2 nor Bax protein expression levels. In conclusion, nicorandil inhibits serum starvation-induced endothelial cell apoptosis possibly through mitochondrial KATP channels.
J Cardiovasc Pharmacol 2005 Dec
PMID:Nicorandil inhibits serum starvation-induced apoptosis in vascular endothelial cells. 1630 93

Although the concept of energy starvation in the failing heart was proposed decades ago, still very little is known about the origin of energetic failure. Recent advances in molecular biology have started to elucidate the transcriptional events governing mitochondrial biogenesis. In particular, a great step was taken with the discovery that peroxisome proliferator-activated receptor gamma co-activator (PGC-1alpha) is the master regulator of mitochondrial biogenesis. The molecular mechanisms underlying the downregulation of PGC-1alpha and the consequent decrease in mitochondrial function in heart failure are, however, still poorly understood. Indeed, the main pathways involved in mitochondrial biogenesis are thought to be up- rather than down-regulated in pathological hypertrophy and heart failure. The current review summarizes recent advances in this field and is restricted to the heart when cardiac data are available.
Cardiovasc Res 2008 Jul 15
PMID:Transcriptional control of mitochondrial biogenesis: the central role of PGC-1alpha. 1843 Jul 51

We recently reported that propargylamine derivatives such as rasagiline (Azilect) and its S-isomer TVP1022 are neuroprotective. The aim of this study was to test the hypothesis that the neuroprotective agents TVP1022 and propargylamine (the active moiety of propargylamine derivatives) are also cardioprotective. We specifically investigated the protective efficacy of TVP1022 and propargylamine in neonatal rat ventricular myocytes (NRVM) against apoptosis induced by the anthracycline chemotherapeutic agent doxorubicin and by serum starvation. We demonstrated that pretreatment of NRVM cultures with TVP1022 or propargylamine attenuated doxorubicin-induced and serum starvation-induced apoptosis, inhibited the increase in cleaved caspase 3 levels, and reversed the decline in Bcl-2/Bax ratio. These cytoprotective effects were shown to reside in the propargylamine moiety. Finally, we showed that TVP1022 neither caused proliferation of the human cancer cell lines HeLa and MDA-231 nor interfered with the anti-cancer efficacy of doxorubicin. These results suggest that TVP1022 should be considered as a novel cardioprotective agent against ischemic insults and against anthracycline cardiotoxicity and can be coadministered with doxorubicin in the treatment of human malignancies.
J Cardiovasc Pharmacol 2008 Sep
PMID:TVP1022 and propargylamine protect neonatal rat ventricular myocytes against doxorubicin-induced and serum starvation-induced cardiotoxicity. 1880 8

Positive caloric balance often causes pathologic adipocyte and adipose tissue anatomical and functional changes (termed adiposopathy or 'sick fat'), which may lead to pathogenic adipocyte and adipose tissue responses and metabolic disease. Fat weight loss may improve adiposopathy, and thus improve metabolic disease in overweight patients. Unfortunately, the efficacy of non-surgical weight loss therapies is often limited due to redundant physiological systems that help 'protect' against starvation and/or negative caloric balance. One strategy to overcome these limitations is to combine weight loss drug therapies having complementary mechanisms of action, thereby affecting more than one physiologic process influencing body fat accumulation. Phentermine is a noradrenergic sympathomimetic amine approved for short-term treatment of obesity. Topiramate is a sulfamate-substituted monosaccharide derivative of the naturally occurring sugar monosaccharide D-fructose approved as a treatment for migraine headaches and seizure disorders. Although known to facilitate weight loss since its approval, topiramate monotherapy does not have a regulatory indication as an anti-obesity agent. Phentermine HCl/topiramate controlled-release (PHEN/TPM CR) is a combination agent containing immediate-release phentermine and controlled-release topiramate. Clinical trials involving thousands of patients demonstrate PHEN/TPM CR to be effective in improving the weight of patients, and also effective in improving adiposopathy-associated metabolic diseases. This review examines the pathophysiology of adiposopathy as a contributor to metabolic disease, the data supporting phentermine monotherapy, topiramate monotherapy and their combination as anti-obesity and anti-adiposopathy agents, and the preliminary evidence supporting PHEN/TPM CR as a generally well-tolerated and effective agent to improve metabolic disease.
Expert Rev Cardiovasc Ther 2010 Dec
PMID:Phentermine, topiramate and their combination for the treatment of adiposopathy ('sick fat') and metabolic disease. 2070 65

Recent clinical studies of therapy for chronic heart failure have yielded unexpected results; for example, only two classes of vasodilators, the converting-enzyme inhibitors and a drug combination that includes nitrates, have so far been shown to improve survival in this lethal condition. Evidence that other vasodilators, as well as most inotropic drugs, worsen prognosis indicates that the underlying problem in chronic heart failure involves more than energy starvation and depressed contractility. These counterintuitive findings can be explained if the fundamental problem in these patients reflects the fact that adult cardiac myocytes are terminally differentiated cells having little or no capacity to divide, so that the shortened life expectancy associated with overload-induced hypertrophy (which I have called the cardiomyopathy of overload) represents an unnatural growth response. Although the mechanism by which chronic overload leads eventually to maladaptive hypertrophy remains speculative, the ability of converting-enzyme inhibitors and nitrates to improve prognosis in heart failure may reflect growth inhibitory effects of these two classes of vasodilator drugs.
Trends Cardiovasc Med
PMID:Scientific insights from clinical studies of converting-enzyme inhibitors in the failing heart. 2123 36

Autophagy is an essential process for the maintenance of cellular homeostasis in the heart under both normal and stress conditions. Autophagy is a key degradation pathway and acts as a quality control sensor. It protects myocytes from cytotoxic protein aggregates and dysfunctional organelles by quickly clearing them from the cell. It also responds to changes in energy demand and mechanical stressors to maintain contractile function. The autophagic-lysosomal pathway responds to serum starvation to ensure that the cell maintains its metabolism and energy levels when nutrients run low. In contrast, excessive activation of autophagy is detrimental to cells and contributes to the development of pathological conditions. A number of signaling pathways and proteins regulate autophagy. These include the 5'-AMP-activated protein kinase/mammalian target of rapamycin pathway, FoxO transcription factors, Sirtuin 1, oxidative stress, Bcl-2 family proteins, and the E3 ubiquitin ligase Parkin. In this review, we will discuss how this diverse cast of characters regulates the important autophagic process in the myocardium.
J Cardiovasc Pharmacol 2012 Aug
PMID:Regulation of autophagy by metabolic and stress signaling pathways in the heart. 2247 7


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