Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan 430060, China.
Cardiovascular Research Institute, Wuhan University, Wuhan 430060, China.
Int J Mol Sci. 2022 Oct 20;23(20):12574. doi: 10.3390/ijms232012574.
Increasing evidence has shown that vascular aging has a key role in the pathogenesis of vascular diseases. P300/CBP-associated factor (PCAF) is involved in many vascular pathological processes, but the role of PCAF in vascular aging is unknown. This study aims to explore the role and underlying mechanism of PCAF in vascular aging. The results demonstrated that the expression of PCAF was associated with age and aging, and remarkably increased expression of PCAF was present in human atherosclerotic coronary artery. Downregulation of PCAF could reduce angiotensin II (AngII)-induced senescence of rat aortic endothelial cells (ECs) in vitro. In addition, inhibition of PCAF with garcinol alleviated AngII-induced vascular senescence phenotype in mice. Downregulation of PCAF could alleviate AngII-induced oxidative stress injury in ECs and vascular tissue. Moreover, PCAF and nuclear factor erythroid-2-related factor 2 (Nrf2) could interact directly, and downregulation of PCAF alleviated vascular aging by promoting the activation of Nrf2 and enhancing the expression of its downstream anti-aging factors. The silencing of Nrf2 with small interfering RNA attenuated the protective effect of PCAF downregulation from vascular aging. These findings indicate that downregulation of PCAF alleviates oxidative stress by activating the Nrf2 signaling pathway and ultimately inhibits vascular aging. Thus, PCAF may be a promising target for aging-related cardiovascular disease.
越来越多的证据表明，血管衰老在血管疾病的发病机制中起着关键作用。P300/CBP 相关因子（PCAF）参与许多血管病理过程，但 PCAF 在血管衰老中的作用尚不清楚。本研究旨在探讨 PCAF 在血管衰老中的作用及其潜在机制。结果表明，PCAF 的表达与年龄和衰老有关，在人动脉粥样硬化性冠状动脉中 PCAF 的表达显著增加。下调 PCAF 可减少体外血管紧张素 II（AngII）诱导的大鼠主动脉内皮细胞（ECs）衰老。此外，用 garcinol 抑制 PCAF 可减轻 AngII 诱导的小鼠血管衰老表型。下调 PCAF 可减轻 AngII 诱导的 ECs 和血管组织氧化应激损伤。此外，PCAF 和核因子红细胞 2 相关因子 2（Nrf2）可以直接相互作用，下调 PCAF 通过促进 Nrf2 的激活和增强其下游抗衰老因子的表达来减轻血管衰老。用小干扰 RNA 沉默 Nrf2 可减弱 PCAF 下调对血管衰老的保护作用。这些发现表明，下调 PCAF 通过激活 Nrf2 信号通路减轻氧化应激，最终抑制血管衰老。因此，PCAF 可能是与衰老相关的心血管疾病的一个有前途的靶点。
