beta-Agonist stimulation produces changes in cardiac AMPK and coronary lumen LPL only during increased workload.
Given the importance of lipoprotein lipase (LPL) in cardiac and vascular pathology, the objective of the present study was to investigate whether the beta-agonist isoproterenol (Iso) influences cardiac LPL. Incubation of quiescent cardiomyocytes with Iso for 60 min had no effect on basal, intracellular, or heparin-releasable (HR)-LPL activity. Similarly, Iso did not change HR-LPL in Langendorff isolated hearts that do not beat against an afterload. In the intact animal, LPL activity at the vascular lumen increased significantly in the Iso-treated group, together with a substantial increase in rate-pressure product. This LPL increase was likely via mechanisms regulated by activation of AMP-activated protein kinase (AMPK) and inactivation of acetyl-CoA carboxylase (ACC280). In glucose-perfused hearts, simply switching from Langendorff to the isolated working heart (that beats against an afterload) induced increases in AMPK and ACC280 phosphorylation and enhanced HR-LPL activity. Provision of insulin and albumin-bound palmitic acid to the working heart was able to reverse these effects. In these hearts, introduction of Iso to the buffer perfusate duplicated the effects seen when this beta-agonist was given in vivo. Our data suggest that Iso can influence HR-LPL only during conditions of increased workload, mechanical performance and excessive energy expenditure, and likely in an AMPK-dependent manner.
An
Ding
D
Faculty of Pharmaceutical Sciences, The Univ. of British Columbia, 2146 East Mall, Vancouver, BC, Canada V6T 1Z3.
Kewalramani
Girsh
G
Qi
Dake
D
Pulinilkunnil
Thomas
T
Ghosh
Sanjoy
S
Abrahani
Ashraf
A
Wambolt
Rich
R
Allard
Michael
M
Innis
Sheila M
SM
Rodrigues
Brian
B
D055372:AMP-Activated Protein Kinases; D000103:Acetyl-CoA Carboxylase / Q000378:metabolism; D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000818:Animals; D015153:Blotting, Western; D004730:Endothelium, Vascular / Q000378:metabolism; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology*; D008071:Lipoprotein Lipase / Q000235:genetics / Q000378:metabolism*; D008297:Male; D009097:Multienzyme Complexes / Q000378:metabolism*; D009200:Myocardial Contraction / Q000187:drug effects / Q000502:physiology; D009206:Myocardium / Q000201:enzymology*; D032383:Myocytes, Cardiac / Q000201:enzymology; D010766:Phosphorylation; D010805:Physical Conditioning, Animal / Q000502:physiology; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D012313:RNA / Q000737:chemistry / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013268:Stimulation, Chemical
D000318:Adrenergic beta-Agonists; D009097:Multienzyme Complexes; D012313:RNA; D017346:Protein Serine-Threonine Kinases; D055372:AMP-Activated Protein Kinases; D008071:Lipoprotein Lipase; D000103:Acetyl-CoA Carboxylase; D007545:Isoproterenol