The role of p53 in atherosclerosis
The role of p53 in atherosclerosis
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DOI：
10.4161/cc.5.17.3166
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发表时间：
2006-09-01
期刊：
影响因子：
4.3
通讯作者：
Bennett, Martin
中科院分区：
文献类型：
--
作者：
Mercer, John;Bennett, Martin
虽然肿瘤抑制基因p53在癌症中的作用是众所周知的，但最近的研究强调了p53在调节晚期动脉粥样硬化斑块中的细胞中的基本作用，动脉粥样硬化斑块是心脏病发作和中风的主要原因。特别是，p53在斑块的复杂环境中被激活，部分是通过病变内的DNA损伤，并调节血管平滑肌细胞（VSMC）的生长停滞、细胞衰老和凋亡。内源性p53的作用已经在发展晚期动脉粥样硬化的小鼠中使用p53敲除来确定，使用骨髓移植来分离对血细胞和血管壁细胞的影响。这些研究产生了明显矛盾和令人惊讶的结果。特别是，最近的研究已经确定了内源性p53在保护VSMCs免于凋亡、在动脉粥样硬化中骨髓基质细胞转分化为VSMCs以及改变斑块中细胞死亡模式中的作用。
Although the role of the tumor suppressor gene p53 is well known in cancer, recent studies have highlighted a fundamental role for p53 in regulating cells in the advanced atherosclerotic plaque, the major cause of heart attacks and stroke. In particular, p53 is activated in the complex environment of the plaque, in part by DNA damage within the lesion, and regulates growth arrest, cell senescence and apoptosis of vascular smooth muscle cells (VSMCs). The role of endogenous p53 has been determined using p53 knockout in mice developing advanced atherosclerosis, using bone marrow transplant to separate effects on blood cells from vessel wall cells. These studies have produced apparently contradictory and surprising results. In particular, recent studies have identified a role for endogenous p53 in protection of VSMCs from apoptosis, trans-differentiation of bone marrow stromal cells into VSMCs in atherosclerosis, and altering the mode of cell death in the plaque.