Lewis Andrew Jm, Neubauer Stefan, Tyler Damian J, Rider Oliver J
a Division of Cardiovascular Medicine, Radcliffe Department of Medicine , University of Oxford , Oxford , OX3 9DU , UK.
b Department of Physiology , Anatomy and Genetics, University of Oxford , Sherrington Road, Oxford , OX3 9DU , UK.
Expert Opin Ther Targets. 2016 Jun;20(6):755-66. doi: 10.1517/14728222.2016.1126248. Epub 2016 Jan 8.
Obesity cardiomyopathy is a major public health problem with few specific therapeutic options. Abnormal cardiac substrate metabolism with reduced pyruvate dehydrogenase (PDH) activity is associated with energetic and functional cardiac impairment and may be a therapeutic target.
This review summarizes the changes to cardiac substrate and high energy phosphorus metabolism that occur in obesity and describes the links between abnormal metabolism and impairment of cardiac function. The available evidence for the currently available pharmacological options for selective metabolic therapy in obesity cardiomyopathy is reviewed.
Pharmacological restoration of PDH activity is in general associated with favourable effects upon cardiac substrate metabolism and function in both animal models and small scale human studies, supporting a potential role as a therapeutic target.
肥胖性心肌病是一个主要的公共卫生问题,几乎没有特定的治疗选择。丙酮酸脱氢酶(PDH)活性降低导致的心脏底物代谢异常与心脏能量和功能损害有关,可能是一个治疗靶点。
本综述总结了肥胖时心脏底物和高能磷代谢的变化,并描述了代谢异常与心脏功能损害之间的联系。综述了目前可用于肥胖性心肌病选择性代谢治疗的药理学选择的现有证据。
在动物模型和小规模人体研究中,PDH活性的药理学恢复通常对心脏底物代谢和功能有有利影响,支持其作为治疗靶点的潜在作用。