Sata Masataka, Tanaka Kimie, Ishizaka Nobukazu, Hirata Yasunobu, Nagai Ryozo
Department of Cardiovascular Medicine, University of Tokyo Graduate School of Medicine, Japan.
Arterioscler Thromb Vasc Biol. 2003 Sep 1;23(9):1548-52. doi: 10.1161/01.ATV.0000089327.48154.32. Epub 2003 Jul 31.
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.
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.
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.
有人提出肿瘤抑制蛋白p53的表达失调可能在闭塞性血管重塑的发病机制中起作用。然而，p53在血管病变中细胞增殖和凋亡中的作用一直存在争议。
我们使用一种可能类似于球囊血管成形术的血管损伤小鼠模型，测试了p53介导的分子信号在病变形成中的潜在作用。将一根粗线插入p53+/+和p53-/-小鼠的股动脉。在快速发生的凋亡（即损伤后4小时）的发生率上没有显著差异。在2周时，p53-/-小鼠病变中增殖细胞的数量显著高于p53+/+小鼠。p53-/-小鼠中凋亡细胞的频率显著低于p53+/+小鼠。在4周时，p53-/-小鼠的内膜增生大于p53+/+小鼠。病变中凋亡频率没有显著差异。
这些结果表明p53在机械损伤后病理性血管重塑中起关键作用，并为开发针对p53的新疗法以预防性治疗血管疾病提供了依据。
