Wild-type p53 gene transfer inhibits neointima formation in human saphenous vein by modulation of smooth muscle cell migration and induction of apoptosis

Patency of autologous human saphenous vein coronary artery bypass grafts (C ABG) is compromised by intimal thickening and superimposed atherosclerosis, caused by migration of vascular smooth muscle cells (SMC) ic? the intima w here they proliferate. Here, using adenoviral transfer, we have targeted SM Cs using wild-type p53 (wt p53) overexpression. initial in vitro analyses d emonstrated that wt p53 overexpression had no effect on SMC proliferation b ut promoted apoptosis, which was inhibited by co-expression of bcl2 or crmA . Wt p53 inhibited SMC invasion through reconstituted matrices, a phenotype not affected by bcl2 or crmA. Overexpression of wt p53 in human saphenous vein before organ culture significantly induced apoptosis (P < 0.01, Studen t's t test) without affecting proliferation rates either in the media or in the intima. SMC migration was, however. significantly reduced by wt p53 (P < 0.01. Student's t test). intimal thickening and the number of neointimal cells were reduced by 89% and 73%, respectively, after 14 days (P < 0.01 a nd P < 0.001, respectively Student's t test). This study demonstrates that overexpression of wt p53 promotes apoptosis and inhibits migration of SMC l eading to reduced intimal thickening. This maybe a useful approach for incr easing patency rates in CABG procedures in the clinic.