Cholesterol induces dedifferentiation of vascular smooth muscle cells by regulating monocyte chemotactic protein-1-induced protein 1.

OBJECTIVE: To discover the effect of cholesterol on dedifferentiation of VSMCs in vitro and the underlying mechanisms. METHODS: Vascular smooth muscle cells (VSMC) were employed to evaluate the role of cholesterol in regulating the dedifferentiation of VSMCs in vitro. Immunofluorescent staining, western blot, and RT-PCR were applied to uncover the inducing effect of cholesterol at a molecular level. RESULTS: We demonstrated that the cholesterol was capable of inducing the dedifferentiation of VSMCs. Mechanistic studies revealed that monocyte chemotactic protein-1-induced protein 1 (MCPIP1) composed the most influential factor in the regulation of VSMCs during the process of cholesterol induction. When MCPIP1 was overexpressed in VSMCs, the dedifferentiation, proliferation and migration of the cells was enhanced, and the expression of miR-145 was suppressed. In contrast, knocking down MCPIP1 by siRNA promoted the differentiation and prohibited the migration of VSMCs after cholesterol treatment. These results demonstrate that MCPIP1 plays an important role in regulating cholesterol-induced dedifferentiation of VSMCs in vitro.