Original ArticleCirculating Mesencephalic Astrocyte-Derived Neurotrophic Factor Negatively Correlates With Atrial Apoptosis in Human Chronic Atrial FibrillationWang, Changhui PhD*; Yu, Shujun BSc†; Bao, Qin MSc‡; Qiang, Weimin MSc§; Wu, Chaoran PhD*; Zhang, Chengxin PhD¶; Jiang, Yan PhD║; Cai, Yongping PhD║; Huang, Dake MSc‡; Chen, Ying PhD‡; Hou, Chao PhD‡; Wang, Dong PhD‡Author Information *Department of Cardiology, The First Affiliated Hospital of Anhui Medical University, Hefei, China; †Second Clinical Medical College, Anhui Medical University, Hefei, People's Republic of China; ‡School of Basic Medical Sciences, Anhui Medical University, Hefei, People's Republic of China; §Department of Pharmacy, Taizhou People's Hospital, Taizhou, People's Republic of China; ¶Department of Cardiac Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, People's Republic of China; and ║Department of Pathology, Anhui Medical University, Hefei, People's Republic of China. Reprints: Dong Wang, PhD, School of Basic Medical Sciences, Anhui Medical University, 81 Meishan Rd, Hefei 230032, Anhui, People's Republic of China (e-mail: firstname.lastname@example.org) or Chao Hou, PhD, School of Basic Medical Sciences, Anhui Medical University, 81 Meishan Rd, Hefei 230032, Anhui, People's Republic of China (e-mail: email@example.com). National Natural Science Foundation of China, Grant Number: 31800702; Grant for Scientific Research of BSKY from Anhui Medical University, Grant Number: XJ201603; Grant from Anhui Medical University, Grant Number: 2017xkj003; Natural Science Foundation of University of Anhui Province, Grant Number: KJ2019A0265; The Youth Fund Project of the First Affiliated Hospital of Anhui Medical University, Grant Number: 2009kj19; Anhui Provincial Natural Science Foundation, Grant Number: 1808085QH239. The authors report no conflicts of interest. Received August 24, 2019 Accepted November 06, 2019 Journal of Cardiovascular Pharmacology: February 2020 - Volume 75 - Issue 2 - p 141-147 doi: 10.1097/FJC.0000000000000781 Buy Metrics Abstract Atrial apoptosis has been found to be majorly involved in the pathogenesis of human atrial fibrillation (AF). Mesencephalic astrocyte-derived neurotrophic factor exerts an antiapoptotic effect for multiple cell types. However, the correlation between MANF and atrial apoptosis in AF is still undefined. In this study, 59 patients with valvular or congenital heart disease were divided into 2 groups: AF group and sinus rhythm (SR) group. We found that the apoptotic atrial myocytes in the right atrial appendage tissues of the AF group were significantly more than those of the SR group, whereas mRNA and protein levels of MANF in the AF group were significantly down-regulated compared with those in the SR group. The serum MANF in patients with AF was markedly lower than that in patients with SR, which was inversely correlated with atrial apoptosis in patients with AF. In addition, the AF group had the greater inflammation and endoplasmic reticulum stress compared with the SR group. These findings suggest that MANF downregulation may lead to more atrial apoptosis in human chronic AF, indicating MANF as a potential therapeutic agent in AF treatment. Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.