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

扩张型心肌病是一组病因不明的左心室功能不全的异质性疾病，具有多种临床病程和病理表现。长链脂肪酸是主要的心脏能量底物之一，了解长链脂肪酸代谢有助于阐明各种心脏疾病的发生机制。心力衰竭大鼠心肌长链脂肪酸代谢降低。虽然低剂量坎地沙坦可以阻断循环血管紧张素引起的血压升高，其程度与高剂量喹普利相同，但它不能提供足够的保护，防止心力衰竭时肾素-血管紧张素系统的损伤。卡维地洛在扩张型心肌病中具有保护心肌肾上腺素能神经元的作用。糖原合成酶激酶（glygen synthase kinase， GSK） 3β是一种正调控心肌凋亡、负调控心肌肥大的多功能蛋白。然而，GSK3β在糖尿病心肌中的作用在很大程度上是未知的。我们发现，注射STZ后3天，GSK3β通过Akt磷酸化降低而变得更活跃（丝氨酸9磷酸化减少），与JNK激活同时发生，这与激活caspase 3和心肌凋亡增加相关。而注射STZ后28 d， GSK3β呈失活状态，与活化T细胞c3核因子核易位、心肌肥大、纤维化等相关。上述参数在14-3-3显性阴性转基因小鼠中均加重。我们的研究结果表明，GSK3β和14-3-3蛋白在糖尿病心肌病的信号传导中起重要作用，氯沙坦或坦宝治疗可以阻止这些变化。

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.