Role of cholesterol-accumulating macrophages on vascular smooth muscle cell proliferation

The proliferation of vascular smooth muscle cells (VSMC) was stimulated by co-incubation with macrophages. Further stimulation was observed when co-incubated macrophages were supplied with LDL or cholesterol. However, the stimulation of VSMC proliferation did not result from co-incubation with macrophages supplemented with acetylated LDL or delipidated LDL. The addition of anti-PDGF antibody partially abolished the stimulation of VSMC proliferation induced by co-incubation with macrophages supplemented with LDL or cholesterol. A high concentration of prostaglandin E2 inhibited the proliferation of VSMC stimulated by PDGF and plasma-derived serum when they were at the G0/G1 stage. However, the inhibitory effect of prostaglandin E2 on proliferation was not observed when cells were incubated with macrophages supplemented with LDL or cholesterol in spite of the promotion under these conditions of prostaglandin E2 production. These results suggest that cholesterol-accumulating macrophages may exert a regulatory effect on the proliferation of VSMC through the synthesis and secretion of platelet-derived growth factor (PDGF) and prostaglandin E2, besides foam-cell formation.