Ang II and PDGF-BB are the key cytokines promoting migration of SMCs in plaque formation. LRP1 inhibits the PDGF-BB–mediated signals for migration and proliferation and/or the modulation of upstream Tsp-1/TGF-β–mediated signals (38) through interaction with the PDGF-β receptor. Ang II induces the Tsp-1/TGF-β signals (37) and LR11 gene transcription through activating AT₁R. LR11 localized on the cell surface becomes the soluble form (as sLR11) by cleavage through TNF-α–converting enzyme (TCE) (22). Circulating sLR11 levels are positively correlated with carotid IMT. sLR11 binds to and interacts with uPAR, the expression of which is mainly regulated by LRP1, on the cell surface and/or on neighboring cells. This complex formation inhibits the internalization of uPAR via LRP1, resulting in enhanced uPAR cell-surface expression. The uPA/uPAR system increases cell mobility through both increased ECM degradation and intracellular integrin/FAK/ERK/Rac-1 signaling, which in turn promotes actin ruffling and myosin isoform switching. The SMCs expressing LR11 display increased migratory capacity in response to PDGF-BB and/or Ang II. Thus, LR11 in combination with its counteracting partner LRP1 regulates the migration of intimal SMCs in injured arteries and atherosclerotic plaques via modulation of the uPA/uPAR system. The proposed LR11-mediated migration of intimal SMCs may be modulated by other Ang II–induced molecules and cytokines, particularly endothelial cell–derived PAI-1 (48). ARBs inhibit (a) the migration of intimal SMCs through downregulation of LR11 and (b) their proliferation by blockade of signals mediated by Tsp-1/TGF-β and PDGF-BB.