Lipoprotein lipase increases low density lipoprotein retention by subendothelial cell matrix.

Abstract

Lipoprotein lipase (LPL), the rate-limiting enzyme for hydrolysis of plasma lipoprotein triglycerides, is a normal constituent of the arterial wall. We explored whether LPL affects (a) lipoprotein transport across bovine aortic endothelial cells or (b) lipoprotein binding to subendothelial cell matrix (retention). When bovine milk LPL was added to endothelial cell monolayers before addition of "2'I-labeled LDL, LDL transport across the monolayers was unchanged; but, at all concentrations of LDL tested (1-100 jig), LDL retention by the monolayers increased more than fourfold. '251-labeled LDL binding to extracellular matrix increased when LPL was added directly to the matrix or was added to the basolateral side ofthe endothelial cell monolayers. Increased LDL binding required the presence of LPL and was not associated with LDL aggregation. LPL also increased VLDL, but not HDL, retention. Monoclonal anti-LPL IgG decreased both VLDL and LDL retention in the presence of LPL. Lipoprotein transport across the monolayers increased during hydrolysis of VLDL triglyceride (TG). In the presence of LPL and VLDL, VLDL transport across the monolayers increased 18% and LDL transport increased 37%. High molar concentrations of oleic acid to bovine serum albumin (3:1) in the medium increased VLDL transport 30%.LDL transport increased 42% when oleic acid was added to the media. Therefore, LPL primarily increased retention of LDL and VLDL. A less remarkable increase in lipoprotein transport was found during hydrolysis of TG-containing lipoproteins. We hypothesize that LPL-mediated VLDL and LDL retention within the arterial wall potentiates conversion of these lipoproteins to more atherogenic forms. (J. Clin. Invest. 1992.89:373-380.)

Overexpression of lipoprotein lipase in transgenic rabbits leads to increased small dense LDL in plasma and promotes atherosclerosis

“…Until now, most studies have focused on whether LPL affects cholesterol-rich remnant clearance in an antiatherogenic manner 6 or whether macrophage-derived LPL in the arterial wall is proatherogenic. 13,14 The antiatherogenic roles of LPL are mainly mediated by the enhanced hepatic clearance of remnant lipoproteins, 15 which leads to lowering plasma cholesterol, 16 whereas the proatherogenic functions of LPL are mainly attributed to the noncatalytic function of vascular cellderived LPL, which may not only promote the retention of atherogenic lipoproteins in the intima 17,18 but also aid in the uptake of lipoproteins by macrophages as well. 19 Moreover, the process of the hydrolysis of TG-rich lipoproteins by LPL also leads to the generation of IDLs and the enhancement of the conversion of large LDLs to small and dense LDLs.…”

Homocysteine Induces Protein Kinase C Activation and Stimulates c-Fos and Lipoprotein Lipase Expression in Macrophages

“…Mo LPL produced in the vascular wall acts as a proatherogenic protein. Indeed, this enzyme mediates the uptake of lipoproteins by Mo (15)(16)(17), promotes lipoprotein retention to the extracellular matrix (18,19), induces the expression of the proatherogenic cytokine tumor necrosis factor-␣ (20,21), increases monocyte adhesion to endothelial cells (22)(23)(24), and increases proliferation of vascular smooth muscle cells (25). Recent evidence shows that Mo LPL promotes foam cell formation and atherosclerosis in vivo (26 -29).…”

Proliferative Effect of Lipoprotein Lipase on Human Vascular Smooth Muscle Cells

“…[7][8][9] Although plasma LPL activity tends to drive lipoprotein metabolism in a nonatherogenic direction, 10 -12 LPL produced in the vascular wall may act as a proatherogenic protein. Indeed, LPL has been shown to mediate uptake of lipoprotein particles by vascular cells, [13][14][15] to promote lipoprotein retention to the extracellular matrix, 16,17 to induce the expression of the proatherogenic cytokine tumor necrosis factor-␣, 18,19 and to enhance monocyte adhesion to endothelial cells. 20,21 Furthermore, recent studies indicate that LPL enhances cellular proteoglycan production 22 and promotes foam cell formation and atherosclerosis in vivo.…”