Department of Cardiology, University of Heidelberg, Heidelberg, Germany.
Autophagy. 2010 Feb;6(2):304-6. doi: 10.4161/auto.6.2.11135. Epub 2010 Feb 6.
The extent of adverse myocardial remodeling contributes essentially to the prognosis after myocardial infarction (MI). Currently, therapeutic strategies that inhibit remodeling are limited to inhibition of neurohumoral activation. mTOR-dependent signaling mechanisms are centrally involved in the myocardial remodeling process. There exists a controversy as to whether autophagy is beneficial in the setting of myocardial infarction. We now provide evidence that induction of autophagy by inhibition of mTOR with everolimus (RAD) prevents adverse left ventricular remodeling and limits infarct size following myocardial infarction. mTOR inhibition increases autophagy and concomitantly decreases proteasome activity especially in the border zone of the infarcted myocardium. The induction of autophagy via mTOR inhibition is a novel potential therapeutic approach to limit infarct size and to attenuate adverse left ventricular remodeling following MI.
心肌重构的程度对心肌梗死后的预后有重要影响。目前，抑制重构的治疗策略仅限于抑制神经体液激活。mTOR 依赖性信号机制在心肌重构过程中起核心作用。自噬在心肌梗死后是否有益存在争议。我们现在提供的证据表明，用依维莫司（RAD）抑制 mTOR 诱导自噬可预防心肌梗死后的不良左心室重构并限制梗死面积。mTOR 抑制增加自噬，同时降低蛋白酶体活性，特别是在梗死心肌的边缘区。通过抑制 mTOR 诱导自噬是一种限制梗死面积和减轻 MI 后不良左心室重构的新的潜在治疗方法。
