Sack Michael N
Center for Molecular Medicine, NHLBI, NIH, Bethesda, MD.
Drug Discov Today Dis Mech. 2013 Jun 1;10(1-2):e41-e46. doi: 10.1016/j.ddmec.2013.05.004.
Obesity is recognized as an independent and increasingly prevalent risk factor for cardiovascular morbidity and mortality. This stems in part from the contribution of obesity towards insulin resistance and diabetes, which associate with premature atherosclerosis, enhanced thrombogenicity and activation of systemic inflammatory programs with resultant cardiovascular dysfunction. This review will focus on the more direct mechanisms underpinning obesity-associated cardiac pathophysiology including the metabolic consequences of lipid accumulation in the myocardium and the consequences of direct systemic effects of lipid toxicity. Furthermore, there is growing recognition that metabolic intermediates, which may be perturbed with caloric excess, may play an important role in intracellular signal transduction and on the post-translational control of metabolic functioning within the heart. As strategies to reverse obesity appear to have ameliorative cardiac effects, surgical and therapeutic approaches to facilitate weight reduction this will also be discussed.
肥胖被认为是心血管疾病发病和死亡的一个独立且日益普遍的危险因素。这部分源于肥胖对胰岛素抵抗和糖尿病的影响,而胰岛素抵抗和糖尿病与过早的动脉粥样硬化、增强的血栓形成性以及系统性炎症程序的激活相关,进而导致心血管功能障碍。本综述将聚焦于肥胖相关心脏病理生理学的更直接机制,包括心肌脂质蓄积的代谢后果以及脂质毒性直接全身效应的后果。此外,人们越来越认识到,可能因热量过剩而受到干扰的代谢中间体,可能在细胞内信号转导以及心脏内代谢功能的翻译后控制中发挥重要作用。由于逆转肥胖的策略似乎具有改善心脏的作用,因此还将讨论促进体重减轻的手术和治疗方法。