Abnormal genes and myocardial fatty acid metabolism in animal with hart dysfunction.

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Dilated cardiomyopathy is a set of heterogeneous diseases of left ventricular dysfunction of unknown etiology, which has a variety of clinical courses and pathological findings. Long-chain fatty acids are one of the major cardiac energy substrates, so understanding long-chain fatty acid metabolism may help in elucidating the mechanisms of various heart diseases. Myocardial long-chain fatty acids metabolism was decreased in rats with heart failure. Although low-dose candesartan can block increases in blood pressure with circulating angiotensin same to the extent as high-close quinapril, it does not confer sufficient protection against injury from the rennin-angiotensin system in heart failure. Carvedilol has beneficial effects and protects cardiac adrenergic neurons in dilated cardiomyopathy.Glycogen synthase kinase (GSK) 3β is a multifunctional protein that positively regulates myocardial apoptosis and negatively regulates hypertrophy. However, the role of GSK3β in the diabetic myocardium is largely unknown. We found that GSK3β became more active (less phosphorylated at serine 9) via decreased Akt phosphorylation, in parallel to JNK activation, which correlated with increased activated caspase 3 and myocardial apoptosis 3 days after streptozotocin (STZ) injection in mice. However, 28 days after STZ injection, GSK3β became inactive, which correlated with the enhanced protein kinase C β2 and p38 MAPK expression, nuclear translocation of nuclear factor of activated T cells c3, cardiac hypertrophy and fibrosis. All of the above parameters were exacerbated in dominant negative 14-3-3 transgenic mice. Our results suggest that GSK3β together with 14-3-3 protein plays essential roles in the signaling of diabetic cardiomyopathy, and treatment with either losartan or tempol prevents these changes.