The absence of p53 accelerates atherosclerosis by increasing cell proliferation in vivo
The absence of p53 accelerates atherosclerosis by increasing cell proliferation in vivo
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DOI：
10.1038/6585
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发表时间：
1999-03-01
期刊：
影响因子：
82.9
通讯作者：
Chan, L
中科院分区：
文献类型：
--
作者：
Guevara, NV;Kim, HS;Chan, L
肿瘤抑制蛋白p53是细胞增殖和程序性细胞死亡（凋亡）的重要分子，并且被认为在动脉粥样硬化的发展中起主要作用。我们研究了p53失活对apoe基因敲除小鼠（动脉粥样硬化动物模型）动脉粥样硬化的影响（1,2）。我们发现，与p53(+/+)/apoE（-/-）小鼠相比，p53(-/-)apoE（-/-）小鼠在高脂肪饮食中存在相似的血清胆固醇时，主动脉粥样硬化的发展速度明显加快。此外，与p53(+/+)/apoE（-/-）小鼠相比，p53(-/-)apoE（-/-）小鼠的动脉粥样硬化病变细胞增殖率显著（类似于280%）增加，细胞凋亡不显著（类似于180%）增加。我们的观察结果表明，p53在动脉粥样硬化病变发展中的作用可能与其在细胞复制控制中的功能有关，并且p53独立的机制可以介导动脉粥样硬化中的凋亡反应。
The tumor suppressor protein p53 is an essential molecule in cell proliferation and programmed cell death (apoptosis), and has been postulated to play a principal part in the development of atherosclerosis. We have examined the effect of p53 inactivation on atherogenesis in apoE-knockout mice, an animal model for atherosclerosis(1,2). We found that, compared with p53(+/+)/apoE(-/-) mice, p53(-/-)apoE(-/-) mice developed considerably accelerated aortic atherosclerosis in the presence of a similar serum cholesterol in response to a high-fat diet. Furthermore, the atherosclerotic lesions in p53(-/-)apoE(-/-) mice had a significant (similar to 280%) increase in cell proliferation rate and an insignificant (similar to 180%) increase in apoptosis compared with those in p53(+/+)/apoE(-/-) mice. Our observations indicate that the role of p53 in atherosclerotic lesion development might be associated with its function in cell replication control, and that p53-independent mechanisms can mediate the apoptotic response in atherosclerosis.