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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2003;23:1548.)
© 2003 American Heart Association, Inc.

Vascular Biology

Absence of p53 Leads to Accelerated Neointimal Hyperplasia After Vascular Injury

Masataka Sata; Kimie Tanaka; Nobukazu Ishizaka; Yasunobu Hirata; Ryozo Nagai

From the Department of Cardiovascular Medicine, University of Tokyo, Graduate School of Medicine, Tokyo, and Precursory Research for Embryonic Science and Technology (M.S.), Japan Science and Technology Corporation, Kawaguchi, Japan.

Correspondence to Dr Masataka Sata, Department of Cardiovascular Medicine, University of Tokyo Graduate School of Medicine, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan. E-mail msata-circ{at}umin.ac.jp

Objective— It has been suggested that deregulated expression of the tumor suppressor protein p53 may play a role in the pathogenesis of occlusive vascular remodeling. However, the role of p53 in cell proliferation and apoptosis in vascular lesions has been controversial.

Methods and Results— We tested the potential involvement of p53-mediated molecular signaling in lesion formation using a mouse model of vascular injury that may resemble balloon angioplasty. A large wire was inserted into the femoral artery of p53^+/+ and p53^-/- mice. There was no significant difference in the occurrence of rapid-onset apoptosis, that is, 4 hours after injury. At 2 weeks, the number of proliferating cells in the lesion of p53^-/- mice was significantly higher than that observed in p53^+/+ mice. The frequency of apoptotic cells was significantly lower in p53^-/- mice than in p53^+/+ mice. At 4 weeks, the neointimal hyperplasia of p53^-/- mice was greater than that of p53^+/+ mice. There was no significant difference in the frequency of apoptosis in the lesions.

Conclusions— These results indicate a crucial role of p53 in pathological vascular remodeling after mechanical injury and provide the basis for the development of new therapies targeting p53 for a prophylactic treatment of vascular diseases.

Key Words: angioplasty • apoptosis • balloon injury • muscle, smooth • atherosclerosis

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