Loss of P53 regresses cardiac remodeling induced by pressure overload partially through inhibiting HIF1α signaling in mice
Loss of P53 regresses cardiac remodeling induced by pressure overload partially through inhibiting HIF1α signaling in mice
复制标题
P53 缺失可部分通过抑制小鼠 HIF1 α 信号传导来逆转由压力超负荷引起的心脏重塑
DOI：
10.1016/j.bbrc.2018.04.225
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发表时间：
2018-06-22
影响因子：
3.1
通讯作者：
Li, Lei
中科院分区：
文献类型：
--
作者：
Li, Jiming;Zeng, Jingjing;Li, Lei
抑癌基因p53被认为是细胞周期和细胞死亡过程中基因组的守护者。P53表达随心肌肥厚向心力衰竭发展而增加，提示p53在心肌重塑中可能起重要作用。在本研究中，在小鼠心脏中缺失p53可以减轻压力超负荷引起的心肌肥厚。使用体内模型研究p53对心脏的作用。用横主动脉结扎术诱导小鼠心肌肥厚。通过超声心动图检查心脏肥大的程度，以及心脏组织的病理和分子分析。小鼠中p53的整体敲除减少了肥大反应，并显著减少了心脏凋亡和纤维化。无p53的心脏对压力超负荷的反应也改善了心脏的射血分数。蛋白质测定进一步表明p53表达的缺失显著增加缺氧诱导因子1-α（HIF 1 α）和血管内皮生长因子（VEGF）的表达。该研究表明，p53通过部分抑制HIF 1 α和VEGF而恶化心脏功能和心脏肥大、凋亡和纤维化。(C)2018爱思唯尔公司All rights reserved.
The tumor suppressor p53 is recognized as the guardian of the genome in cell cycle and cell death. P53 expression increases as cardiac hypertrophy worsens to heart failure, suggesting that p53 may play important role in cardiac remodeling. In the present study, deletion of p53 in the mice heart would ameliorate cardiac hypertrophy induced by pressure overload. The role of p53 on heart was investigated using in vivo models. Cardiac hypertrophy in mice was induced by transverse aortic banding surgery. The extent of cardiac hypertrophy was examined by echocardiography, as well as pathological and molecular analyses of heart tissue. Global knockout of p53 in the mice reduced the hypertrophic response and markedly reduced cardiac apoptosis, and fibrosis. Ejection fraction of heart was also improved in hearts without p53 in response to pressure overload. Protein determination further suggested loss of p53 expression markedly increased Hypoxia-inducible factor 1-alpha (HIF1 alpha) and vascular endothelial growth factor (VEGF) expression. The study indicated p53 deteriorated cardiac functions and cardiac hypertrophy, apoptosis, and fibrosis by partially inhibition of HIF1 alpha and VEGF. (C) 2018 Elsevier Inc. All rights reserved.