p53-induced inhibition of Hif-1 causes cardiac dysfunction during pressure overload

摘要

心脏增大或心肌肥大是对工作量增大的一种生理反应，帮助维持心脏 功能。然而，如果这种状况时间长了，它会发展成心脏衰竭。在用一 个心肌肥大小鼠模型所做的一项研究中，研究人员对这种转变是如何 发生的有了新的认识。当实验动物心脏增大时，会形成新的血管来支 持它。但大约两星期后，肿瘤抑制蛋白P53会在心脏细胞中积累，血 管形成被阻断，小鼠出现心脏衰竭。通过抑制P53或通过促进血管形 成来影响这一过程，也许可以成为阻止心肌肥大向心脏衰竭发展的一 种手段。%Cardiac hypertrophy occurs as an adaptive response to increased workload to maintain cardiac function. However, prolonged cardiac hypertrophy causes heart failure, and its mechanisms are largely unknown. Here we show that cardiac angiogenesis is crucially involved in the adaptive mechanism of cardiac hypertrophy and that p53 accumulation is essential for the transition from cardiac hypertrophy to heart failure. Pressure overload initially promoted vascular growth in the heart by hypoxia-inducible factor-1 (Hif-1)-dependent induction of angiogenic factors, and inhibition of angiogenesis prevented the development of cardiac hypertrophy and induced systolic dysfunction.