Published online before print May 6, 2004, doi: 10.1161/01.ATV.0000131260.80316.37
© 2004 American Heart Association, Inc.
Atherosclerosis and Lipoproteins |
Human Smooth Muscle Cell Subpopulations Differentially Accumulate Cholesteryl Ester When Exposed to Native and Oxidized Lipoproteins
From the Vascular Biology Group at the Robarts Research Institute (C.A.A., C.G.S., S.L., Z.N., J.G.P., M.W.H.), and the Departments of Medicine (C.G.S., R.A.H., J.G.P., M.W.H.) and Biochemistry (R.A.H., J.G.P., M.W.H.), University of Western Ontario, London, Ontario, Canada.
Correspondence to Murray W. Huff, Robarts Research Institute, Room 4-16, 100 Perth Drive, London, Ontario, Canada, N6A 5K8. E-mail mhuff{at}uwo.ca
Background— Vascular smooth muscle cells (SMCs) manifest diverse phenotypes and emerging evidence suggests this is caused by inherently distinct SMC subtypes. Recently, Li et al (Circ Res 2001;89:517–525) successfully cloned 2 uniquely responsive SMC subpopulations from a single human artery and we used this unique resource to test the hypothesis that distinct SMC subtypes are differential precursors of foam cell formation.
Methods and Results— When challenged with human atherogenic native or oxidized hypertriglyceridemic very-low-density lipoprotein (HTG-VLDL), the larger, slower-growing, spindle-shaped HITB5 SMC clone accumulated significantly more cholesteryl ester (CE) and triglyceride (TG) than the smaller, faster-growing epithelioid-shaped HITA2 SMC clone (10 versus 2 µg CE/mg cell protein [PN] and 60 versus 7 µg TG/mg PN, P<0.05). Lipoprotein lipase (LPL), a key enzyme involved in lipoprotein uptake, was identified as one differentially expressed protein that altered the predisposition of HITA2 SMCs for lipid accumulation. Although HITB5 SMCs secreted significantly more LPL than did HITA2 SMCs (0.7 versus 0.2 U/mL media, P<0.05), the addition of bovine milk LPL to HITA2 SMCs, significantly increased native and oxidized HTG-VLDL–induced lipid accumulation.
Conclusions— Inherently distinct SMC subsets are differentially predisposed to lipoprotein-induced lipid accumulation. Moreover, the environment can influence the response of SMC subsets to atherogenic lipoproteins.
We tested whether epithelioid and spindle-shaped human SMCs differentially accumulated lipid on exposure to native and oxidized lipoproteins. Spindle-shaped HITB5 cells preferentially accumulated cholesteryl ester and triglyceride, whereas the epithelioid-like HITA2 SMCs required exogenous LPL to accumulate lipid in the presence of lipoproteins. Therefore, SMC subtypes are differentially predisposed to a lipid-accumulating phenotype.
Key Words: atherosclerosis • lipoproteins • smooth muscle cells • foam cells
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