Abstract：
Aerobic training (AT), an effective form of cardiac rehabilitation, has been shown to be beneficial for cardiac repair and remodeling after myocardial infarction (MI). The p300/CBP-associated factor (PCAF) is one of the most important lysine acetyltransferases and is involved in various biological processes. However, the role of PCAF in AT and AT-mediated cardiac remodeling post-MI has not been determined. Here, we found that the PCAF protein level was significantly increased after MI, while AT blocked the increase in PCAF. AT markedly improved cardiac remodeling in mice after MI by reducing endoplasmic reticulum stress (ERS). In vivo, similar to AT, pharmacological inhibition of PCAF by Embelin improved cardiac recovery and attenuated ERS in MI mice. Furthermore, we observed that both IGF-1, a simulated exercise environment, and Embelin protected from H2O2-induced cardiomyocyte injury, while PCAF overexpression by viruses or the sirtuin inhibitor nicotinamide eliminated the protective effect of IGF-1 in H9C2 cells. Thus, our data indicate that maintaining low PCAF levels plays an essential role in AT-mediated cardiac protection, and PCAF inhibition represents a promising therapeutic target for attenuating cardiac remodeling after MI.
摘要：
有氧训练(AT)一种有效的心脏康复方法,已被证明对心肌梗死（MI）后的心脏修复和重塑有益。p300/CBP相关因子（PCAF）是最重要的赖氨酸乙酰转移酶之一，参与各种生物学过程。然而,PCAF在AT和AT介导的MI后心脏重构中的作用尚未确定.这里,我们发现PCAF蛋白水平在MI后显著升高,而AT阻断了PCAF的增加。AT通过减少内质网应激（ERS）显着改善MI后小鼠的心脏重塑。在体内,类似于AT,Embelin对PCAF的药理抑制作用可改善MI小鼠的心脏恢复并减轻ERS。此外，我们观察到IGF-1，一种模拟的运动环境，和Embelin免受H2O2诱导的心肌细胞损伤，而病毒或沉默酶抑制剂烟酰胺的PCAF过表达消除了IGF-1在H9C2细胞中的保护作用。因此，我们的数据表明，维持低PCAF水平在AT介导的心脏保护中起着至关重要的作用，和PCAF抑制代表了减轻MI后心脏重塑的有希望的治疗目标。
