Feng-Chun Tsai1, Yen-Chen Lin2, Shang-Hung Chang2, Gwo-Jyh Chang3, Yu-Juei Hsu4, Yuan-Min Lin5, Yun-Shien Lee6, Chun-Li Wang2, Yung-Hsin Yeh7. 1. Division of Cardiac Surgery, Chang-Gung Memorial Hospital, Chang-Gung University College of Medicine, Taoyuan, Taiwan. 2. Cardiovascular Division, Chang-Gung Memorial Hospital, Chang-Gung University College of Medicine, Taoyuan, Taiwan. 3. Graduate Institute of Clinical Medical Sciences, Chang-Gung University College of Medicine, Chang-Gung University, Taiwan. 4. Division of Nephrology, Department of Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan. 5. School of Dentistry, National Yang-Ming University, Taipei, Taiwan. 6. Department of Biotechnology, Ming-Chuan University, Taoyuan, Taiwan. 7. Cardiovascular Division, Chang-Gung Memorial Hospital, Chang-Gung University College of Medicine, Taoyuan, Taiwan. Electronic address: yeongshinn@cgmh.org.tw.
Abstract
BACKGROUND: Atrial fibrillation (AF) causes atrial remodeling, and the left atrium (LA) is the favored substrate for maintaining AF. It remains unclear if AF remodels both atria differently and contributes to LA arrhythmogenesis and thrombogenesis. Therefore, we wished to characterize the transcript profiles in the LA and right atrium (RA) in sinus rhythm (SR) and AF respectively. METHODS: Paired LA and RA appendages acquired from patients receiving cardiac surgery were used for ion-channel- and whole-exome-based transcriptome analysis. The ultrastructure was evaluated by immunohistochemistry. RESULTS: Twenty-two and twenty ion-channels and transporters were differentially expressed between the LA and RA in AF and SR, respectively. Among these, 15 genes were differentially expressed in parallel between AF and SR. AF was associated with increased LA/RA expression ratio in 9 ion channel-related genes, including genes related to calcium handling. In microarray, AF was associated with a differential LA/RA gene expression ratio in 309 genes, and was involved in atherosclerosis-related signaling. AF was associated with the upregulation of thrombogenesis-related genes in the LA appendage, including P2Y12, CD 36 and ApoE. Immunohistochemistry showed higher expressions of collagen-1, oxidative stress and TGF-β1 in the RA compared to the LA. CONCLUSIONS: AF was associated with differential LA-to-RA gene expression related to specific ion channels and pathways as well as upregulation of thrombogenesis-related genes in the LA appendage. Targeting the molecular mechanisms underlying the LA-to-RA difference and AF-related remodeling in the LA appendage may help provide new therapeutic options in treating AF and preventing thromboembolism in AF.
BACKGROUND:Atrial fibrillation (AF) causes atrial remodeling, and the left atrium (LA) is the favored substrate for maintaining AF. It remains unclear if AF remodels both atria differently and contributes to LA arrhythmogenesis and thrombogenesis. Therefore, we wished to characterize the transcript profiles in the LA and right atrium (RA) in sinus rhythm (SR) and AF respectively. METHODS: Paired LA and RA appendages acquired from patients receiving cardiac surgery were used for ion-channel- and whole-exome-based transcriptome analysis. The ultrastructure was evaluated by immunohistochemistry. RESULTS: Twenty-two and twenty ion-channels and transporters were differentially expressed between the LA and RA in AF and SR, respectively. Among these, 15 genes were differentially expressed in parallel between AF and SR. AF was associated with increased LA/RA expression ratio in 9 ion channel-related genes, including genes related to calcium handling. In microarray, AF was associated with a differential LA/RA gene expression ratio in 309 genes, and was involved in atherosclerosis-related signaling. AF was associated with the upregulation of thrombogenesis-related genes in the LA appendage, including P2Y12, CD 36 and ApoE. Immunohistochemistry showed higher expressions of collagen-1, oxidative stress and TGF-β1 in the RA compared to the LA. CONCLUSIONS:AF was associated with differential LA-to-RA gene expression related to specific ion channels and pathways as well as upregulation of thrombogenesis-related genes in the LA appendage. Targeting the molecular mechanisms underlying the LA-to-RA difference and AF-related remodeling in the LA appendage may help provide new therapeutic options in treating AF and preventing thromboembolism in AF.
Authors: Alison M Thomas; Claudia P Cabrera; Malcolm Finlay; Kulvinder Lall; Muriel Nobles; Richard J Schilling; Kristie Wood; Charles A Mein; Michael R Barnes; Patricia B Munroe; Andrew Tinker Journal: Physiol Genomics Date: 2019-06-07 Impact factor: 3.107
Authors: Catherine E Lipovsky; Jesus Jimenez; Qiusha Guo; Gang Li; Tiankai Yin; Stephanie C Hicks; Somya Bhatnagar; Kentaro Takahashi; David M Zhang; Brittany D Brumback; Uri Goldsztejn; Rangarajan D Nadadur; Carlos Perez-Cervantez; Ivan P Moskowitz; Shaopeng Liu; Bo Zhang; Stacey L Rentschler Journal: JCI Insight Date: 2020-09-17