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Current Pharmaceutical Design
ISSN (Print): 1381-6128
ISSN (Online): 1873-4286
VOLUME: 19
ISSUE: 27
DOI: 10.2174/1381612811319270006      Price:  $58









PPARγ Activation Improves the Molecular and Functional Components of Ito Remodeling by Angiotensin II

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Author(s): Gayani Nanayakkara, Nilmini Viswaprakash, Juming Zhong, Thiruchelvan Kariharan, John Quindry and Rajesh Amin
Pages 4839-4847 (9)
Abstract:
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 (Ito) 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 Ito current. In the current study, we explored the protective effect of PPARγ ligands on cardiomyocyte Ito by preventing NADPH Oxidase activation and the ensuing ROS formation. Furthermore, short term PPARγ activation in diabetic leptin deficient db/db mice displayed improvements in the membrane association of the molecular components of Ito as well as prolonged QT interval. These findings demonstrate that PPARγ agonists have the potential to attenuate cardiomyocyte dysfunction associated with diabetes.
Keywords:
Diabetes, cardiac remodeling, PPARγ; transient outward potassium channel current, Ito.
Affiliation:
Dept. of Pharmacal Sciences, 326 West Thach Ave, 3211E Walker Building, Auburn University, Auburn, Alabama 36849.