EXPRESSION OF P53 PROTEIN AND P53 GENE TRANSCRIPTS IN RABBIT CAROTID ARTERIES AFTER BALLOON DENUDATION

Smooth muscle cell (SMC) proliferation may be positively or negatively regulated by various factors after arterial wall injury. We investiga ted the hypothesis that the p53 protein may play a role in regulating SMC proliferation. We examined p53 protein expression and p53 gene tra nscript distribution in rabbit carotid arteries over a period of 6 wee ks after balloon denudation in relation to SMC proliferation. The numb er of p53-positive SMCs in the neointima reached a maximum 2 weeks aft er balloon denudation when proliferating SMCs decreased and were confi ned to the luminal surface of the intima. The p53-positive SMCs in the neointima almost paralleled the distribution of proliferating cell nu clear antigen (PCNA)-positive SMCs but not that of Ki-67-positive cell s. Double immunofluorescence showed the simultaneous nuclear localizat ion of both p53 protein and PCNA in intimal SMCs. Strong signals for p 53 gene transcripts, identified by in situ hybridization, were observe d in SMCs showing positive immunostaining for p53 protein. Our results indicate that p53 protein and p53 gene transcript levels increase, ar e closely Linked to the proliferation of SMCs in the thickened intima, and play a key role in the regulation of cell proliferation during th e repair process after arterial wall injury.