AUTHOR=Tu Tao , Qin Fen , Bai Fan , Xiao Yichao , Ma Yingxu , Li Biao , Liu Na , Zhang Baojian , Sun Chao , Liao Xiaobo , Zhou Shenghua , Liu Qiming TITLE=Quantitative acetylated proteomics on left atrial appendage tissues revealed atrial energy metabolism and contraction status in patients with valvular heart disease with atrial fibrillation JOURNAL=Frontiers in Cardiovascular Medicine VOLUME=Volume 9 - 2022 YEAR=2022 URL=https://www.frontiersin.org/journals/cardiovascular-medicine/articles/10.3389/fcvm.2022.962036 DOI=10.3389/fcvm.2022.962036 ISSN=2297-055X ABSTRACT=Background: Numerous basic studies have demonstrated the critical roles of metabolic and contractile remodeling in the pathophysiological changes of atrial fibrillation (AF), but acetylation changes underlying the atrial remodeling have not been fully elucidated. Quantitative acetylated proteomics enables researchers to identify a comprehensive map of protein alterations in hearts of patients responsible for the pathological developing progresses of AF. Methods: In this study, 18 samples (9 with chronic AF and 9 with sinus rhythm) of left atrial appendage (LAA) tissues were obtained during the mitral valve replacement surgery. The changes of the quantitative acetylated proteome between the AF and sinus rhythm (SR) group were studied using dimethyl-labeling, acetylation affinity enrichment and high performance liquid chromatography-tandem mass spectrometry analysis. Results: We identified a total of 5,007 acetylated sites on 1,330 acetylated proteins, among which 352 acetylated sites on 193 acetylated proteins were differentially expressed between AF and SR group by setting quantification ratio of 1.3 for threshold value and P < 0.05 for significant statistical difference. Bioinformatics analysis showed that these differentially expressed acetylated proteins were mainly involved in energy metabolism and cellular contraction and structure function related biological processes and pathways. Among the 87 differentially expressed energy metabolism acetylated proteins related to the processes of fatty acid, carbohydrate, ketone body metabolism and oxidative phosphorylation, nearly 87.1% Kac sites were up-regulated (148 Kac sites among 170) in AF group. Besides, generally declining acetylation of cardiac muscle contraction related proteins (88.9% Kac sites of myosin) was found in the LAA of AF patient. Immune coprecipitation combined with western blotting was used to validate the differential expression of acetylated proteins. Conclusion: Plenty of differential expressed energy metabolism and cellular contraction acetylated proteins were found in the LAA tissues from chronic AF patients, which may reflected the impaired ATP production capacity and decreased atrial muscle contractility in atrial during AF. Thus, acetylation may play an important regulatory role in metabolic and contractile remodeling of atrial during AF. Moreover, the identified new acetylated sites and proteins may become the promising targets for the prevention and treatment of AF.