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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2000;20:2212.)
© 2000 American Heart Association, Inc.

Vascular Biology

Proliferative Effect of Lipoprotein Lipase on Human Vascular Smooth Muscle Cells

Jean-Claude Mamputu; Luc Levesque; Geneviève Renier

From the CHUM Research Center, Notre-Dame Hospital, Department of Nutrition (J.-C.M., G.R.), and Laboratory of Molecular Cardiology (L.L.), University of Montreal, Quebec, Canada.

Correspondence to Dr Geneviève Renier, CHUM Research Center, Notre-Dame Hospital, J.-A. De Seve Pavilion, Door Y 3622, 1560 Sherbrooke St E, Montreal, Quebec, Canada H2L 4M1. E-mail renierg{at}ere.umontreal.ca

Abstract—Vascular smooth muscle cell (VSMC) proliferation is a key event in the development and progression of atherosclerotic lesions. Accumulating evidence suggests that lipoprotein lipase (LPL) produced in the vascular wall may exert proatherogenic effects. The aim of the present study was to examine the effect of LPL on VSMC proliferation. Incubation of growth-arrested human VSMCs with purified endotoxin-free bovine LPL for 48 and 72 hours, in the absence of any added exogenous lipoproteins, resulted in a dose-dependent increase in VSMC growth. Addition of VLDLs to the culture media did not further enhance the LPL effect. Treatment of growth-arrested VSMCs with purified human or murine LPL (1 µg/mL) led to a similar increase in cell proliferation. Neutralization of bovine LPL by the monoclonal 5D2 antibody, irreversible inhibition, or heat inactivation of the lipase suppressed the LPL stimulatory effect on VSMC growth. Moreover, preincubation of VSMCs with the specific protein kinase C inhibitors calphostin C and chelerythrine totally abolished LPL-induced VSMC proliferation. In LPL-treated VSMCs, a significant increase in protein kinase C activity was observed. Treatment of VSMCs with heparinase III (1 U/mL) totally inhibited LPL-induced human VSMC proliferation. Taken together, these data indicate that LPL stimulates VSMC proliferation. LPL enzymatic activity, protein kinase C activation, and LPL binding to heparan sulfate proteoglycans expressed on VSMC surfaces are required for this effect. The stimulatory effect of LPL on VSMC proliferation may represent an additional mechanism through which the enzyme contributes to the progression of atherosclerosis.

Key Words: lipoprotein lipase • vascular smooth muscle cell • protein kinase C • proteoglycans • atherosclerosis

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