Zhang Yi, Chen Huan-Xin, Hou Hai-Tao, Liu Ying-Qi, Chen Zhuo, Yang Qin, He Guo-Wei
Department of Cardiovascular Surgery & The Institute of Cardiovascular Diseases, TEDA International Cardiovascular Hospital, Tianjin University & Chinese Academy of Medical Sciences, Tianjin, China.
Tianjin Key Laboratory of Molecular Regulation of Cardiovascular Diseases and Translational Medicine, Tianjin, China.
Commun Biol. 2025 Jun 4;8(1):858. doi: 10.1038/s42003-025-08264-9.
Lysine propionylation modification (Kpr) plays an important role in the pathogenesis of several cardiovascular diseases, but the role of Kpr in postoperative atrial fibrillation (POAF) is unclear. Here, we established an atlas of proteomics and propionylation proteomics in the atrial appendage tissues from 28 CABG patients, exploring the role of Kpr proteins in the occurrence of POAF. The Kpr of ALDH6A1 was most significantly increased on Lys113 (2.25 folds). The activity of ALDH6A1 increased due to higher binding energy of propionylated ALDH6A1 and NAD, causing an increase in NADH levels in cells and triggering abnormal energy metabolism. Furthermore, the increase in NADH levels triggered the accumulation of reactive oxygen species, which may cause oxidative stress, resulting in the development of AF. This study reveals the important role of ALDH6A1-NADH pathway in POAF, and provides new insights for exploring the pathogenesis of POAF in CABG.
赖氨酸丙酰化修饰(Kpr)在多种心血管疾病的发病机制中起重要作用,但Kpr在术后房颤(POAF)中的作用尚不清楚。在此,我们建立了28例冠状动脉旁路移植术(CABG)患者心耳组织的蛋白质组学和丙酰化蛋白质组学图谱,探讨Kpr蛋白在POAF发生中的作用。ALDH6A1在赖氨酸113位点的丙酰化修饰增加最为显著(2.25倍)。丙酰化的ALDH6A1与烟酰胺腺嘌呤二核苷酸(NAD)结合能更高,导致ALDH6A1活性增加,引起细胞内烟酰胺腺嘌呤二核苷酸磷酸(NADH)水平升高并触发能量代谢异常。此外,NADH水平升高引发活性氧的积累,这可能导致氧化应激,从而导致房颤的发生。本研究揭示了ALDH6A1-NADH途径在POAF中的重要作用,并为探索CABG患者POAF的发病机制提供了新的见解。