Oxidative modifications of LDL increase its binding to extracellular matrix from human aortic intima: influence of lesion development, lipoprotein lipase and calcium

Retention of atherogenic lipoproteins in the arterial intima by extracellul ar matrix (ECM) is assumed to occur during early atherogenesis and its furt her development. Low density lipoprotein (LDL) trapped in the intima may un dergo oxidative modifications, which initiate a chain reaction in atherogen esis. Lipoprotein lipase (LPL) has been found to mediate the binding of nat ive and oxidized LDL to ECM produced by cultured cells and to contribute to foam cell formation by mildly oxidized LDL. In this study ECM, isolated fr om human aortic intima with different atherosclerotic lesions, was used for the first time to measure the binding to it in vitro of native and differe ntly oxidized I-125-LDL. Oxidation of I-125-LDL increased its binding to th e ECM, which was most prominent with the material isolated from intima at t he early stage of atherogenesis. With the progression of atherosclerosis, t he ability of the isolated intimal ECM to bind native and oxidized I-125-LD L decreased, and strongly oxidized I-125-LDL decreased more than native and moderately oxidized I-125-LDL. LPL increased the binding of moderately oxi dized I-125-LDL to the ECM more than native I-125-LDL, while it had only a small effect on strongly oxidized I-125-LDL. LPL-mediated binding of native and oxidized I-125-LDL decreased with the development of atherosclerotic l esions. Calcium ions also increased the binding of LDL to the ECM. This enh anced binding increased with the extent of LDL oxidation, especially at the early stage of atherogenesis, and decreased with lesion progression. These data suggest that the ability of ECM to retain LDL in arterial intima depe nds on LDL oxidation status and changes with the progression of atherogenes is. In addition, LPL and calcium ions may participate in the retention of L DL in vivo. Copyright (C) 2001 John Wiley & Sons, Ltd.