Cardiac Energy Metabolism in Heart Failure.
Cardiac Energy Metabolism in Heart Failure.
复制标题
DOI：
10.1161/circresaha.121.318241
复制
发表时间：
2021-05-14
影响因子：
20.1
通讯作者：
Abel ED
中科院分区：
文献类型：
--
作者：
Lopaschuk GD;Karwi QG;Tian R;Wende AR;Abel ED
心脏能量代谢的改变会加重心力衰竭的严重程度。然而，心力衰竭时发生的能量代谢变化是复杂的，不仅取决于现有心力衰竭的严重程度和类型，还取决于常见合并症（如肥胖和2型糖尿病）的共存情况。衰竭的心脏面临能量不足，这主要是由于线粒体氧化能力下降所致。糖酵解产生的三磷酸腺苷（ATP）增加对此进行了部分补偿。用于线粒体ATP生产的不同燃料的相对贡献也发生了变化，包括葡萄糖和氨基酸氧化减少，以及酮体氧化增加。心脏对脂肪酸的氧化增加还是减少，取决于心力衰竭的类型。例如，在与糖尿病和肥胖相关的心力衰竭中，心肌脂肪酸氧化增加，而在与高血压或缺血相关的心力衰竭中，心肌脂肪酸氧化减少。综合起来，这些能量代谢变化导致衰竭的心脏效率降低（即心脏做功/耗氧量下降）。衰竭心脏中糖酵解和线粒体氧化代谢的改变，既是由于这些代谢途径中关键酶的转录变化，也是由于氧化还原状态（NAD⁺和NADH水平）的改变以及代谢物信号传导的改变，这些改变导致了编码能量代谢酶的基因表达的翻译后表观遗传变化。除了通过糖酵解或葡萄糖氧化的通量之外，葡萄糖去向的改变也会导致心力衰竭的病理变化。重要的是，针对能量代谢途径的药物靶向治疗已成为一种新的治疗方法，可提高衰竭心脏的心脏效率、减少能量不足并改善心脏功能。
Alterations in cardiac energy metabolism contribute to the severity of heart failure. However, the energy metabolic changes that occur in heart failure are complex, and are dependent not only on the severity and type of heart failure present, but also on the co-existence of common co-morbidities such as obesity and type 2 diabetes. The failing heart faces an energy deficit, primarily due to a decrease in mitochondrial oxidative capacity. This is partly compensated for by an increase in ATP production from glycolysis. The relative contribution of the different fuels for mitochondrial ATP production also changes, including a decrease in glucose and amino acid oxidation, and an increase in ketone oxidation. The oxidation of fatty acids by the heart increases or decreases, depending on the type of heart failure. For instance, in heart failure associated with diabetes and obesity, myocardial fatty acid oxidation increases, while in heart failure associated with hypertension or ischemia, myocardial fatty acid oxidation decreases. Combined, these energy metabolic changes result in the failing heart becoming less efficient (i.e., a decrease in cardiac work/O2 consumed). The alterations in both glycolysis and mitochondrial oxidative metabolism in the failing heart are due to both transcriptional changes in key enzymes involved in these metabolic pathways, as well as alterations in redox state (NAD+ and NADH levels) and metabolite signaling that contribute to post-translational epigenetic changes in the control of expression of genes encoding energy metabolic enzymes. Alterations in the fate of glucose, beyond flux through glycolysis or glucose oxidation, also contribute to the pathology of heart failure. Of importance, pharmacological targeting of the energy metabolic pathways has emerged as a novel therapeutic approach to improving cardiac efficiency, decreasing the energy deficit and improving cardiac function in the failing heart.
DOI：
10.1038/oby.2008.414
发表时间：
2008-12
期刊：
Obesity (Silver Spring, Md.)
影响因子：
--
作者：
Thakker GD;Frangogiannis NG;Zymek PT;Sharma S;Raya JL;Barger PM;Taegtmeyer H;Entman ML;Ballantyne CM
通讯作者：
Ballantyne CM
影响因子：
4.4
作者：
Oda M;Wakabayashi S;Ari Wijetunga N;Yuasa S;Enomoto H;Kaneda R;Yoon SH;Mittal N;Jing Q;Suzuki M;Greally JM;Fukuda K;Makino S
通讯作者：
Makino S