Circulating triglyceride lipolysis facilitates lipoprotein lipase translocation from cardiomyocyte to myocardial endothelial lining

doi:10.1016/S0008-6363(03)00469-3

Circulating triglyceride lipolysis facilitates lipoprotein lipase translocation from cardiomyocyte to myocardial endothelial lining

Thomas Pulinilkunnil,
Dake Qi,
Sanjoy Ghosh,
Claudia Cheung,
Patsy Yip,
Jospy Varghese,
Ashraf Abrahani,
Roger Brownsey and
Brian Rodrigues* (rodrigue{at}unixg.ubc.ca)

Division of Pharmacology and Toxicology, Faculty of Pharmaceutical Sciences and The Department of Biochemistry, The University of British Columbia, 2146 East Mall, Vancouver, British Columbia V6T 1Z3, Canada

*Corresponding author. Tel.: +1-604-822-4758; fax: +1-604-822-3035.

Received February 25, 2003.
Revision requested May 23, 2003.
Accepted May 28, 2003.

Abstract

Objective: Lipoprotein lipase (LPL) mediated hydrolysis of circulating triglyceride (TG)-rich lipoproteins provides the heart with fatty acids. The present study was designed to investigate the influence of circulating TG and their lipolysis in facilitating translocation of LPL from the underlying cardiomyocyte cell surface to the coronary lumen. Methods: The in vivo effects of diazoxide (DZ), an agent that causes rapid hypoinsulinemia, and the in vitro effect of the lipoprotein breakdown product l-α-lysophosphatidylcholine (Lyso-PC) on luminal LPL were examined in Wistar rats. Manipulation of circulating TG in DZ-treated animals and their influence on LPL was also determined. Results: Within 4 h following DZ a major increase in LPL activity and protein occurred at the coronary lumen. Myocyte cell surface LPL was reduced 50% subsequent to DZ. Exposure of isolated control hearts to 1 nM Lyso-PC enhanced luminal LPL to levels observed following DZ. Treatment of DZ animals with either WR 1339 (inhibits circulating TG breakdown) or N⁶-cyclopentyladenosine (inhibits adipose tissue lipolysis) decreased DZ induced augmentation of cardiac LPL. Conclusions: Using DZ, our studies for the first time demonstrate that LPL at the coronary lumen can be augmented as early as 4 h after hypoinsulinemia and that this increase likely involves posttranslational processing via TG breakdown of circulating lipoproteins and a Lyso-PC dependent mechanism.

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