Division of Cardiology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
Eur J Heart Fail. 2012 Feb;14(2):120-9. doi: 10.1093/eurjhf/hfr173.
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.
在过去的几十年中，心力衰竭的发病率和患病率显著增加。现有数据表明，心力衰竭患者的病因各不相同，但都存在有活力但功能失调的心肌，这些心肌具有潜在的可挽救性。尽管大量研究都集中在心力衰竭的分子基础上，但心脏代谢在该疾病中仍然是一个研究不足的领域。已知心力衰竭中许多心肌细胞能量学的方面都发生了改变。这些改变包括从脂肪酸向葡萄糖作为首选底物的转变，以及 ATP 水平的下降。尽管有这些已证实的变化，但目前尚无针对心力衰竭代谢酶或蛋白的批准药物。这部分是由于我们对调节心脏代谢的机制和途径的了解有限。更好地描述这些途径可能会为心力衰竭的治疗带来新的疗法。针对有活力和潜在可挽救组织中的心肌能量学可能是心力衰竭治疗的特别有效方法。在这里，我们将回顾心力衰竭中脂肪酸和葡萄糖代谢以及 AMP 激活的蛋白激酶中发生的代谢变化。我们提出，心脏能量学应该被视为心力衰竭治疗的潜在靶点，并且应该在该领域进行更多的研究。
