Published online before print March 21, 2002, doi: 10.1161/01.RES.0000016164.02525.B4
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© 2002 American Heart Association, Inc.
Molecular Medicine |
CD36 Mediates the Cardiovascular Action of Growth Hormone-Releasing Peptides in the Heart
From the Faculty of Pharmacy and Department of Pharmacology (V.B., N.M., P.P., D.L., A.D., A.P, H.O.), Université de Montréal, Montreal, Canada; the Division of Hematology and Medical Oncology, Department of Medicine (M.F., R.L.S.), Weill Medical College, Cornell University, New York, NY; Biovitrum AB (T.S.), Stockholm, Sweden; and the Department of Pharmacology (E.E.), Université de Sherbrooke, Canada.
Correspondence to Dr Huy Ong, Faculty of Pharmacy, Université de Montréal, C.P. 6128, Succursale Centre-ville, Montreal, Quebec, H3C 3J7 Canada. E-mail huy.ong{at}umontreal.ca
Growth hormone-releasing peptides (GHRPs) are known as potent growth hormone secretagogues whose actions are mediated by the ghrelin receptor, a G protein-coupled receptor cloned from pituitary libraries. Hexarelin, a hexapeptide of the GHRP family, has reported cardiovascular activity. To identify the molecular target mediating this activity, rat cardiac membranes were labeled with a radioactive photoactivatable derivative of hexarelin and purified using lectin affinity chromatography and preparative gel electrophoresis. A binding protein of Mr 84 000 was identified. The N-terminal sequence determination of the deglycosylated protein was identical to rat CD36, a multifunctional glycoprotein, which was expressed in cardiomyocytes and microvascular endothelial cells. Activation of CD36 in perfused hearts by hexarelin was shown to elicit an increase in coronary perfusion pressure in a dose-dependent manner. This effect was lacking in hearts from CD36-null mice and hearts from spontaneous hypertensive rats genetically deficient in CD36. The coronary vasoconstrictive response correlated with expression of CD36 as assessed by immunoblotting and covalent binding with hexarelin. These data suggest that CD36 may mediate the coronary vasospasm seen in hypercholesterolemia and atherosclerosis.
Key Words: acute coronary syndromes • growth hormone-releasing peptides • CD36 scavenger receptor
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