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 incidence and prevalence of heart failure have increased significantly over the past few decades. Available data suggest that patients with heart failure independent of the aetiology have viable but dysfunctional myocardium that is potentially salvageable. Although a great deal of research effort has focused on characterizing the molecular basis of heart failure, cardiac metabolism in this disorder remains an understudied discipline. It is known that many aspects of cardiomyocyte energetics are altered in heart failure. These include a shift from fatty acid to glucose as a preferred substrate and a decline in the levels of ATP. Despite these demonstrated changes, there are currently no approved drugs that target metabolic enzymes or proteins in heart failure. This is partly due to our limited knowledge of the mechanisms and pathways that regulate cardiac metabolism. Better characterization of these pathways may potentially lead to new therapies for heart failure. Targeting myocardial energetics in the viable and potentially salvageable tissue may be particularly effective in the treatment of heart failure. Here, we will review metabolic changes that occur in fatty acid and glucose metabolism and AMP-activated kinase in heart failure. We propose that cardiac energetics should be considered as a potential target for therapy in heart failure and more research should be done in this area.
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PMID:Targeting myocardial substrate metabolism in heart failure: potential for new therapies. 2225 53

Although disruption of leptin signaling is associated with obesity as well as cardiac lipid accumulation and dysfunction, it has been difficult to separate the direct effects of leptin on the heart from those associated with the effects of leptin on body weight and fat mass. Using Cre-loxP recombinase technology, we developed tamoxifen-inducible, cardiomyocyte-specific leptin receptor-deficient mice to assess the role of leptin in regulating cardiac function. Cre recombinase activation in the heart resulted in transient reduction in left ventricular systolic function which recovered to normal levels by day 10. However, when cardiomyocyte leptin receptors were deleted in the setting of Cre recombinase-induced left ventricular dysfunction, irreversible lethal heart failure was observed in less than 10 days in all mice. Heart failure after leptin receptor deletion was associated with marked decreases of cardiac mitochondrial ATP, phosphorylated mammalian target of rapamycin (mTOR), and AMP-activated kinase (pAMPK). Our results demonstrate that specific deletion of cardiomyocyte leptin receptors, in the presence of increased Cre recombinase expression, causes lethal heart failure associated with decreased cardiac energy production. These observations indicate that leptin plays an important role in regulating cardiac function in the setting of cardiac stress caused by Cre-recombinase expression, likely through actions on cardiomyocyte energy metabolism.
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PMID:Cardiomyocyte-specific deletion of leptin receptors causes lethal heart failure in Cre-recombinase-mediated cardiotoxicity. 2311 24

Diabetic cardiomyopathy (DCM) is a common cardiovascular complication of diabetic mellitus that is characterized by diastolic disorder in the early stage and clinical heart failure in the later stage. Presently, DCM is considered one of the major causes of death in diabetic patients. Resveratrol (RSV), a naturally occurring stilbene, is widely reported as a cardioprotective substance in many heart diseases. Thus far, the specific roles of RSV in DCM prevention and treatment have attracted great attention. Here, we discuss the roles of RSV in DCM by focusing its downstream targets from both in vivo and in vitro studies. Among such targets, Sirtuins 1/3 and AMP-activated kinase have been identified as key mediators that induce cardioprotection during hyperglycemia. In addition, many other signaling molecules (e.g., forkhead box-O3a and extracellular regulated protein kinases) are also regulated in the presence of RSV and exert beneficial effects such as opposing oxidative stress, inflammation, and apoptosis in cardiomyocytes exposed to high-glucose conditions. The beneficial potential of an RSV/stem cell cotherapy is also reviewed as a promising therapeutic strategy for preventing the development of DCM.
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PMID:Resveratrol and Diabetic Cardiomyopathy: Focusing on the Protective Signaling Mechanisms. 3225 59