(Left) In stable atherosclerosis, lesional macrophages clearing apoptotic cells produce TGFβ, IL-10, and SPMs. These pro-resolving molecules bind to receptors present on the surface of vSMCs that drive Myocardin/SRF binding to CArG boxes, which promote the expression of genes associated with vSMC quiescence. This can be further enhanced by the interaction between vSMCs and the surrounding ECM through integrins α1β1, α2β1, α3β1, and α7β1. (Right) Plaques vulnerable to rupture contain macrophages with impaired efferocytosis, which leads to the secretion of the proinflammatory cytokines TNFα, IL-1β, and IL-6. These bind to their cognate receptors in vSMCs and downregulate Myocardin expression. Inflammatory cytokines also stimulate the association of KLF4 to G/C elements that prevent SRF binding to CArG boxes. Interactions between vSMCs and the ECM proteins fibronectin, fibrinogen, and vitronectin cause NFκB and NFAT activation and promotes the expression of MMPs and inflammatory genes.