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.
Current Pharmaceutical Design
Title:PPARγ Activation Improves the Molecular and Functional Components of Ito Remodeling by Angiotensin II
Volume: 19 Issue: 27
Author(s): Gayani Nanayakkara, Nilmini Viswaprakash, Juming Zhong, Thiruchelvan Kariharan, John Quindry and Rajesh Amin
Affiliation:
Keywords: Diabetes, cardiac remodeling, PPARγ; transient outward potassium channel current, Ito.
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.
Export Options
About this article
Cite this article as:
Nanayakkara Gayani, Viswaprakash Nilmini, Zhong Juming, Kariharan Thiruchelvan, Quindry John and Amin Rajesh, PPARγ Activation Improves the Molecular and Functional Components of Ito Remodeling by Angiotensin II, Current Pharmaceutical Design 2013; 19 (27) . https://dx.doi.org/10.2174/1381612811319270006
DOI https://dx.doi.org/10.2174/1381612811319270006 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
A Comprehensive Review on Ethnomedicinal, Pharmacological and Phytochemical Basis of Anticancer Medicinal Plants of Pakistan
Current Cancer Drug Targets Phenotypic Characterization of a Family With An In-frame Deletion in the DMD Gene and Variable Penetrance
Current Gene Therapy Stairway to Heaven or Hell? Perspectives and Limitations of Chagas Disease Chemotherapy
Current Topics in Medicinal Chemistry Molecular Modeling Investigation of Some New 2-mercaptoimidazoles
Current Computer-Aided Drug Design MicroRNAs and Cardiac Conduction
Current Drug Targets Autoantibodies for Cardiac Channels and Sudden Cardiac Death and its Relationship to Autoimmune Disorders
Current Cardiology Reviews Red Cell Glycolytic Enzyme Disorders Caused by Mutations: An Update
Cardiovascular & Hematological Disorders-Drug Targets Big Data and Genome Editing Technology: A New Paradigm of Cardiovascular Genomics
Current Cardiology Reviews Unravelling the Role of Infectious Agents in the Pathogenesis of Human Autoimmunity: The Hypothesis of the Retroviral Involvement Revisited
Current Molecular Medicine Atherosclerotic and Non-Atherosclerotic Coronary Heart Disease in Women
Current Medicinal Chemistry Transient Receptor Potential Channels - Emerging Novel Drug Targets for the Treatment of Pain
Current Medicinal Chemistry Clinical Vignettes: Integrated Care of Cancer Patients by Oncologists and Cardiologists
Current Cardiology Reviews Pituitary Dysfunction as a Cause of Cardiovascular Disease
Current Pharmaceutical Design TTR Fibril Formation Inhibitors: Is there a SAR?
Current Medicinal Chemistry Bariatric Surgery: Indications, Safety and Efficacy
Current Pharmaceutical Design The Potential Role of Claudins in Regulation of Metastasis and Development of Drug Resistance in Breast Cancer
Clinical Cancer Drugs Magnetic Resonance-Based Metabolomics for Understanding Neurological Disorders: Current Status and Statistical Considerations
Current Metabolomics Limitations of Current Antiretroviral Agents and Opportunities for Development
Current Pharmaceutical Design A Glance on the Role of Bacterial Siderophore from the Perspectives of Medical and Biotechnological Approaches
Current Drug Targets Serelaxin: New Investigational Treatment in Acute Heart Failure
Cardiovascular & Hematological Agents in Medicinal Chemistry