Transfer of Wild-Type p53 Gene Effectively Inhibits Vascular Smooth Muscle Cell Proliferation In Vitro and In Vivo

Abstract—Wild-type p53 (wt-p53), a key protein in cell cycle regulation, inactivates the G1 cyclins through direct activation of p21Waf-1/Cip-1/Sdi-1. Persistent vascular smooth muscle cell (VSMC) proliferation following vascular interventions hinders the benefits of these therapeutics. Using the hemagglutinating virus of Japan/liposome–mediated gene transfer method, we examined the inhibitory effect of overexpression of exogenous wt-p53 on VSMC proliferation in vitro and in vivo. We assessed the proliferative activity of human p53 cDNA–transduced bovine VSMCs by DNA synthesis assay, flow cytometry, and cell proliferation assay. p53 gene transfer reduced thymidine incorporation of VSMCs stimulated by platelet-derived growth factor-BB (P<.001). The p53-transduced VSMCs underwent synthetic phase depletion (mean, 8.02% versus 33.7% of control; P<.001) and transient G2/M accumulation 2 days after gene transfection, and in almost all cells, G1 arrest occurred (mean, 92.6% versus 79.3% of control; P<.001) 5 day...