Modulation of the Cardiomyocyte Hypertrophic Responses to Endothelin-1 by Adipocytes

Leptin and adiponectin are the adipokines that are shown to exert pro-hypertrophic and anti-hypertrophic effects respectively, in cardiomyocytes. We sought to determine the direct interaction between the adipocytes and cardiomyocytes during endothelin-1 (ET-1)-induced cardiomyocyte hypertrophy and determine the role of leptin and adiponectin. The adipose tissue conditioned medium (ACM) inhibited the ET-1-induced hypertrophy in a concentration-dependent manner and this anti-hypertrophic effect was more potent or reversed in the presence of leptin receptor antagonist (LRA; 0.1 nM) or adiponectin receptor-1 antibody (ARA; 100 ng/mL), respectively. ACM from heart failure rats induced by coronary artery ligation or obese rats did not mitigate the ET-1 induced hypertrophy in cardiomyocytes. These studies demonstrate that the net anti-hypertrophic activity of ACM in ET-1-induced cardiac hypertrophy is likely mediated by adiponectin due activation of AMPK and determined by the leptin to adiponectin ratio. Heart failure and obese-induced pathology changes the characteristics of adipocytes although the underlying mechanisms for this effect are not completely known.

Name thesis:degree_name

M Sc

Discipline thesis:degree_discipline

Physiology and Pharmacology

Grantor dc:publisher

The University of Western Ontario

Year dc:date.issued

2014

Author dc:creator

• Bairwa, Suresh Chandra

Advisor dc:contributor.advisor

• Morris Karmazyn

• Cardiac hypertrophy
• heart failure
• cardiomyocytes
• leptin
• adiponectin
• ACM
• adipocytes
• ET-1
• obesity

Language dc:language.iso

en_ca

Handle dc:identifier.uri

https://hdl.handle.net/20.500.14721/35488

OAI identifier oai:identifier

oai:uwo.scholaris.ca:20.500.14721/35488