Effect of p53 deficiency on external vascular cuff-induced neointima formation.

The p53 tumor suppressor gene may act as an inhibitor of vascular neointima formation in response to injury and in the present study the effects of p53 deficiency on external vascular cuff-induced neointima formation were evaluated. Vascular neointima formation was induced by an external vascular cuff; a polyethylene tube placed around a 2 mm segment of the left femoral artery ensheathed the adventitia, but avoided direct intraluminal injury. Two weeks after cuff placement, the cuff-sheathed and contralateral control arteries without cuff from wild-type (n=10) and p53 deficient (n=8) mice were harvested and analyzed by quantitative morphometry. The areas of the lumen, intima, and media were measured in 10 cross-sections from one edge to the other of the cuffed portion, and in the corresponding 2-mm segment of the contralateral control artery. The volume ratio of the intima to media (I/M) was calculated. The contralateral control arteries without a cuff did not have intima in either wild-type or p53 deficient mice. In the cuff-sheathed arteries, neointima formation of p53 deficient mice with an I/M of 93% was significantly greater than that of wild-type mice with an I/M of 50% (P=0.001). The absence of p53 is associated with increased neointima formation in response to cuff injury.