Taegtmeyer Heinrich, Wilson Christopher R, Razeghi Peter, Sharma Saumya
University of Texas Health Science Center, Department of Internal Medicine, Division of Cardiology, Houston, Texas 77030, USA.
Ann N Y Acad Sci. 2005 Jun;1047:208-18. doi: 10.1196/annals.1341.019.
From the first stages of differentiation in the embryo to the end of life, energy substrate metabolism and function are inextricably linked features of the heart. The principle of energy substrate metabolism is simple. For a given developmental stage and for a given environment, the heart oxidizes the most efficient fuel on the path to ATP. The "multitasking" of energy substrate metabolism in the heart entails more than the generation of reducing equivalents for oxidative phosphorylation of ADP in the respiratory chain. In the postnatal heart, substrate switching and metabolic flexibility are features of normal function. In the stressed heart, metabolic remodeling precedes, triggers, and sustains functional and structural remodeling. This manuscript reviews the pleiotropic actions of metabolism in energy transfer, signal transduction, cardiac growth, gene expression, and viability. Examples are presented to illustrate that metabolic signals of stressed and failing heart are the product of complex cellular processes. An early feature of the maladapted heart is a loss of metabolic flexibility. The example of lipotoxic heart failure illustrates the concept of sustained metabolic dysregulation as a cause of contractile dysfunction of the heart. Thus, a paradigm emerges in which metabolic signals not only regulate fluxes through enzyme catalyzed reactions in existing metabolic pathways, but also regulate transcriptional, translational, and post-translational signaling in the heart. As new insights are gained into metabolic adaptation and maladaptation of the heart, metabolic modulation may become an effective strategy for the treatment of heart failure.
从胚胎分化的最初阶段到生命结束，能量底物代谢和功能都是心脏紧密相连的特征。能量底物代谢的原理很简单。对于给定的发育阶段和给定的环境，心脏会氧化通往ATP过程中最有效的燃料。心脏中能量底物代谢的“多任务”功能不仅仅是为呼吸链中ADP的氧化磷酸化生成还原当量。在出生后的心脏中，底物转换和代谢灵活性是正常功能的特征。在应激状态下的心脏中，代谢重塑先于、触发并维持功能和结构重塑。本文综述了代谢在能量转移、信号转导、心脏生长、基因表达和生存能力方面的多效性作用。文中列举了一些例子来说明应激和衰竭心脏的代谢信号是复杂细胞过程的产物。适应不良心脏的一个早期特征是代谢灵活性丧失。脂毒性心力衰竭的例子说明了持续代谢失调作为心脏收缩功能障碍原因的概念。因此，出现了一种范式，即代谢信号不仅调节现有代谢途径中酶催化反应的通量，还调节心脏中的转录、翻译和翻译后信号传导。随着对心脏代谢适应和适应不良有了新的认识，代谢调节可能成为治疗心力衰竭的有效策略。
