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 investigated the hypothesis that the p53 protein may play a role in regulating SMC proliferation. We examined p53 protein expression and p53 gene transcript distribution in rabbit carotid arteries over a period of 6 weeks after balloon denudation in relation to SMC proliferation. The number of p53-positive SMCs in the neointima reached a maximum 2 weeks after balloon denudation when proliferating SMCs, decreased and were confined to the luminal surface of the intima. The p53-positive SMCs in the neointima almost paralleled the distribution of proliferating cell nuclear antigen (PCNA)-positive SMCs but not that of Ki-67-positive cells. Double immunofluorescence showed the simultaneous nuclear localization of both p53 protein and PCNA in intimal SMCs. Strong signals for p53 gene transcripts, identified by in situ hybridization, were observed in SMCs showing positive immunostaining for p53 protein. Our results indicate that p53 protein and p53 gene transcript levels increase, are closely linked to the proliferation of SMCs in the thickened intima, and play a key role in the regulation of cell proliferation during the repair process after arterial wall injury.