Wang Zhao V, Li Dan L, Hill Joseph A
*Department of Internal Medicine, Division of Cardiology, University of Texas Southwestern Medical Center, Dallas, TX; and †Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX.
J Cardiovasc Pharmacol. 2014 Apr;63(4):302-13. doi: 10.1097/FJC.0000000000000054.
Heart failure is a leading cause of morbidity and mortality worldwide, currently affecting 5 million Americans. A syndrome defined on clinical terms, heart failure is the end result of events occurring in multiple heart diseases, including hypertension, myocardial infarction, genetic mutations and diabetes, and metabolic dysregulation, is a hallmark feature. Mounting evidence from clinical and preclinical studies suggests strongly that fatty acid uptake and oxidation are adversely affected, especially in end-stage heart failure. Moreover, metabolic flexibility, the heart's ability to move freely among diverse energy substrates, is impaired in heart failure. Indeed, impairment of the heart's ability to adapt to its metabolic milieu and associated metabolic derangement are important contributing factors in the heart failure pathogenesis. Elucidation of molecular mechanisms governing metabolic control in heart failure will provide critical insights into disease initiation and progression, raising the prospect of advances with clinical relevance.
心力衰竭是全球发病和死亡的主要原因，目前影响着500万美国人。心力衰竭是一种根据临床症状定义的综合征，是多种心脏病（包括高血压、心肌梗死、基因突变和糖尿病）以及代谢失调所引发事件的最终结果，代谢失调是其标志性特征。临床和临床前研究的越来越多证据有力地表明，脂肪酸摄取和氧化受到不利影响，尤其是在终末期心力衰竭中。此外，代谢灵活性，即心脏在多种能量底物之间自由转换的能力，在心力衰竭中受损。事实上，心脏适应其代谢环境的能力受损以及相关的代谢紊乱是心力衰竭发病机制中的重要促成因素。阐明心力衰竭中代谢控制的分子机制将为疾病的发生和发展提供关键见解，从而带来具有临床相关性进展的前景。
