LRP1B is a negative modulator of increased migration activity of intimal smooth muscle cells from rabbit aortic plaques

Abstract

The migration of cultured cultured smooth muscle cells (SMCs) is regulated by the time-specific expression of members of the LDL receptor family (LRs). LRP1B, a member of LRs, modulates the catabolism of PDGF β-receptor, affecting the migration of SMCs. An involvement of PDGF β-receptor in atherosclerosis is focused because of its abundant expression in intimal SMCs. Here, in order to know a functional significance of LRP1B in the increased migration of intimal SMCs, the functions of three groups of cultured SMCs with different origins in atherosclerotic arteries were studied. Each group of SMCs (central, marginal or medial SMCs) was isolated from explanted pieces of central or marginal area of thickened intima, or media prepared from rabbit aortic plaques. The LRP1B expression levels were significantly decreased in intimal SMCs, particularly in marginal SMCs, compared to medial SMCs. The expression levels of LRP1B in SMCs were negatively correlated with those of PDGF β-receptor. The level of PDGF β-receptor-mediated phosphorylation of ERK 1/2 in central SMCs was increased to 5.2-fold with the functional inhibition of LRP1B using anti-LRP1B IgY. The antibody increased the PDGF-BB-stimulated migration and invasion activities in SMCs. The increase in the PDGF β-receptor-mediated outgrowth activity of SMCs from the explants was also inhibited by the functional inhibition of LRP1B. These results indicate that LRP1B regulated the migration activity of SMCs through the modulation of PDGF β-receptor-mediated pathway. The regulation of LRP1B expression is possibly involved in the activated migration of intimal SMCs in the course of atherosclerosis.