PKR deficiency delays vascular aging via inhibiting GSDMD-mediated endothelial cell hyperactivation

被引：4
|
作者：
Peng, Zhouyangfan [1 ]
Tan, Xiqing [2 ]
Xie, Liangpeng [3 ]
Li, Ze [3 ]
Zhou, Sufang [4 ]
Li, Yapei [1 ]
机构：
[1] Cent South Univ, Xiangya Hosp 3, Dept Hlth Management Ctr, Changsha, Peoples R China
[2] Cent South Univ, Xiangya Hosp 3, Dept Gen Practice, Changsha, Peoples R China
[3] Cent South Univ, Xiangya Hosp 3, Dept Hematol & Crit Care Med, Changsha, Peoples R China
[4] Guangxi Med Univ, Sch Basic Med Sci, Nanning, Peoples R China
来源：
ISCIENCE | 2023年 / 26卷 / 01期
基金：
中国国家自然科学基金;
关键词：
ACTIVATION; MECHANISMS;
D O I：
10.1016/j.isci.2022.105909
中图分类号：
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号：
07 ; 0710 ; 09 ;
摘要：
Vascular aging is an independent risk factor for cardiovascular diseases, but the regulatory mechanism is not clearly understood. In this study, we found that endothelial PKR activity is elevated in aging aorta tissues, which is accompanied with increased endothelial cell hyperactivation, IL-beta and HMGB1 release and vascular smooth muscle cell (VSMC) phenotype transforming. Global knockout of PKR exhibits significantly delayed vascular aging compared to wild-type mice at the same age. In vitro, using PKR siRNA or the cell hyperactivation inhibitor glycine or disulfiram can effectively inhibit H2O2 or palmitic acid-induced endothelial cell hyperactivation, IL-10 and HMGB1 release and co-cultured VSMC phenotype transforming. These results demonstrate that endothelial PKR activation induces GSDMD-mediated endothelial cell hyperactivation to release HMGB1 and IL-beta, which promotes the phenotype transforming of VSMC and subsequent accelerates the process of vascular aging. These discoveries will help to explore the new drug target to inhibit vascular aging.
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收藏
页数：18
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