Human coronary smooth muscle cells internalize versican-modified LDL through LDL receptorrelated protein and LDL

Abstract—Versican-like proteoglycans are the main component of the intimal extracellular matrix interacting with low density lipoprotein (LDL). The aim of this study has been to investigate the receptors involved in versican-modified LDL uptake by human vascular smooth muscle cells (VSMCs). We have found that versican-LDL interaction leads to the following: (1) monomeric LDL particles that are similar in size and electrophoretic mobility to native LDL but that have a higher capacity to induce intracellular cholesteryl ester (CE) accumulation and (2) fused LDL particles similar in size to those obtained by vortexing. The precipitable fraction of versican-LDL, composed of 50 % monomeric and 50 % fused LDL particles, induced a dose-response increase in the CE content of VSMCs. Anti–LDL receptor antibody decreased the CE accumulation derived from monomeric LDL particles by 883 % and that derived from the total precipitable fraction by 453%. Inhibition of LDL receptor–related protein expression by antisense oligodeoxynucle-otides reduced the CE accumulation derived from the precipitable fraction by 652.8%, whereas it did not produce any effect on the CE accumulation derived from monomeric LDL. These results suggest that versican-LDL induces CE accumulation in human VSMCs by the LDL receptor (monomeric particles) and LDL receptor–related protein (fused LDL). (Arterioscler Thromb Vasc Biol. 2002;22:387-393.) Key Words: vascular smooth muscle cells LDL receptor–related protein versican cholesteryl ester accumulation antisense oligodeoxynucleotide