PPARγ Activation Improves the Molecular and Functional Components of Ito Remodeling by Angiotensin II
PPARγ Activation Improves the Molecular and Functional Components of Ito Remodeling by Angiotensin II
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DOI：
10.2174/1381612811319270006
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发表时间：
2013-08-01
影响因子：
3.1
通讯作者：
Amin, Rajesh
中科院分区：
文献类型：
--
作者：
Nanayakkara, Gayani;Viswaprakash, Nilmini;Amin, Rajesh
Patients with diabetes exhibit significantly altered renin-angiotensin system (RAS) control. Recently, it has been determined that hyperglycemic conditions induce an increase in angiotensin II (AT II) expression; specifically by cardiomyocytes. Altered RAS has been shown to be associated with an increase in oxidative stress and cardiac dysfunction leading to the development of cardiac hypertrophy. The transient outward potassium current (I-to) in cardiac myocytes is mainly mediated by members of the Kv subfamily of voltage gated potassium channels and has been shown to be altered in cellular localization and expression during the development of cardiac hypertrophy. However it is not clear as to how AT II affects the pore forming complex at the cell membrane and thus directly affects the I-to current. In the current study, we explored the protective effect of PPAR gamma ligands on cardiomyocyte I-to by preventing NADPH Oxidase activation and the ensuing ROS formation. Furthermore, short term PPAR gamma activation in diabetic leptin deficient db/db mice displayed improvements in the membrane association of the molecular components of I-to as well as prolonged QT interval. These findings demonstrate that PPAR gamma agonists have the potential to attenuate cardiomyocyte dysfunction associated with diabetes.
