The genetic basis for the phenotypic switching of vascular smooth muscle cells (VSMCs) is unclear in
atherosclerosis. Recent studies showed that the 21-base pair deletion mutation (Δ21) in
myocyte enhancer factor 2A (MEF2A) gene could be an inherited marker for
coronary artery disease. MEF2A mutation may affect the phenotypic switching of VSMCs. Human aortic VSMCs were used. Four groups of VSMCs transfected with
green fluorescent protein plasmid (control group), MEF2A wild-type (WT) plasmid (WT group), MEF2A Δ21 plasmid (Δ21 group) or MEF2A
siRNA (
siRNA group) were studied. The proliferation of VSMCs was determined by methylthiazolyldiphenyl-tetrazolium
bromide, and the migration of VSMCs was measured by Millicell chamber. The
protein expressions of MEF2A, smooth muscle α-actin, SM22α,
osteopontin and
p38 mitogen-activated protein kinase signaling pathway were detected by Western blotting.
MEF2A protein expression was knockdown by
siRNA transfection.
MEF2A protein was overexpressed in WT and Δ21 groups. Δ21 and
siRNA groups obviously showed more proliferation (methylthiazolyldiphenyl-tetrazolium
bromide, 0.63 vs 0.66 vs 0.31, P < 0.01) and migration (52.6 vs 58.0 vs 21.2, P < 0.01) of VSMCs as compared with the WT group. In addition, the transfection of Δ21 and
siRNA could induce the down-regulation of smooth muscle α-actin and SM22α (P < 0.01) and the up-regulation of
osteopontin (P < 0.01) in VSMCs. The phosphorylated p38 signaling pathway expression was significantly enhanced in the Δ21 and
siRNA groups as compared with that of the WT group (P < 0.01). These results suggest that MEF2A dominant negative mutation and
RNA silence could induce the phenotypic switching of VSMCs, leading to its increased proliferation and migration, and
p38 mitogen-activated protein kinase signaling pathway may participate in it.