首页 | 本学科首页   官方微博 | 高级检索  
   检索      


Cardiomyocyte Aldose Reductase Causes Heart Failure and Impairs Recovery from Ischemia
Authors:Ni-Huiping Son  Radha Ananthakrishnan  Shuiqing Yu  Raffay S Khan  Hongfeng Jiang  Ruiping Ji  Hirokazu Akashi  Qing Li  Karen O'Shea  Shunichi Homma  Ira J Goldberg  Ravichandran Ramasamy
Institution:1. Department of Medicine, Columbia University Medical Center, New York, New York, United States of America.; 2. Department of Medicine, New York University School of Medicine, New York, New York, United States of America.; Bristol Heart Institute, University of Bristol, United Kingdom,
Abstract:Aldose reductase (AR), an enzyme mediating the first step in the polyol pathway of glucose metabolism, is associated with complications of diabetes mellitus and increased cardiac ischemic injury. We investigated whether deleterious effects of AR are due to its actions specifically in cardiomyocytes. We created mice with cardiac specific expression of human AR (hAR) using the α–myosin heavy chain (MHC) promoter and studied these animals during aging and with reduced fatty acid (FA) oxidation. hAR transgenic expression did not alter cardiac function or glucose and FA oxidation gene expression in young mice. However, cardiac overexpression of hAR caused cardiac dysfunction in older mice. We then assessed whether hAR altered heart function during ischemia reperfusion. hAR transgenic mice had greater infarct area and reduced functional recovery than non-transgenic littermates. When the hAR transgene was crossed onto the PPAR alpha knockout background, another example of greater heart glucose oxidation, hAR expressing mice had increased heart fructose content, cardiac fibrosis, ROS, and apoptosis. In conclusion, overexpression of hAR in cardiomyocytes leads to cardiac dysfunction with aging and in the setting of reduced FA and increased glucose metabolism. These results suggest that pharmacological inhibition of AR will be beneficial during ischemia and in some forms of heart failure.
Keywords:
设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司  京ICP备09084417号