Int J Physiol Pathophysiol Pharmacol 2009;1(1):1-14.
Original Article The effect of caveolin-1 (Cav-1) on fatty acid uptake and CD36 localization and lipotoxicity in vascular smooth muscle (VSM) cells
Heather M. Mattern, Leena S. Raikar, and Christopher D. Hardin
Department of Medical Pharmacology and Physiology, University of Missouri, Columbia, MO 65212
Received October 3, 2008; accepted November 4, 2008; available online November 20, 2008
Abstract: The purpose of this study was to determine whether Cav-1 is involved in lipotoxicity in VSM cells by altering CD36 membrane localization. Normal A7r5 cells, Cav-1 overexpressing cells, and cells treated with 10 mM cyclodextrin for 30 minutes were immunolabeled with Cav-1 and CD36. The peripheral to central ratio of CD36 in Cav-1 overexpressing cells (1.52±0.19) was significantly higher than in control cells (1.05±0.16) and cyclodextrin-treated cells (0.861±0.279). Fatty acid uptake at different time points was quantified with C1-BODIPY 500/510 C12 fluorescence. A7r5 VSM cells overexpressing Cav-1 had decrease in the rate of fatty acid uptake compared to control cells. Cells treated with cyclodextrin also had a decrease in fatty acid uptake compared to control. Cav-1 overexpressing cells incubated in 0.05 mM palmitate had 31.4±8.8% apoptosis, where only 3.9±1.0% of Cav-1 overexpressing cells incubated in albumin were apoptotic. Cyclodextrin treatment resulted in a decrease in apoptosis in cells incubated in 0.1 mM palmitate (69.7±2.1%) compared to control cells incubated in palmitate (85.6±2.7%). These data suggest that in cells overexpressing Cav-1, CD36 is relocated to the plasma membrane of VSM cells, where it may play an increased role in fatty acid uptake and possibly lipotoxicity. (IJPPP810001).
Address all correspondence to: Christopher D. Hardin, PhD Department of Medical Pharmacology and Physiology MA415 Medical Sciences Building University of Missouri Columbia, MO 65212 Phone: (573) 884-6209 Fax: (573) 884-6209 E-mail: hardinc@missouri.edu