title: Differential left-to-right atria gene expression ratio in human sinus rhythm and atrial fibrillation: Implications for arrhythmogenesis and thrombogenesis.
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.
authors: Division of Cardiac Surgery, Chang-Gung Memorial Hospital, Chang-Gung University College of Medicine, Taoyuan, Taiwan.
authors: Feng-Chun
authors: FC
authors: Tsai
authors: Cardiovascular Division, Chang-Gung Memorial Hospital, Chang-Gung University College of Medicine, Taoyuan, Taiwan.
authors: Yen-Chen
authors: YC
authors: Lin
authors: Cardiovascular Division, Chang-Gung Memorial Hospital, Chang-Gung University College of Medicine, Taoyuan, Taiwan.
authors: Shang-Hung
authors: SH
authors: Chang
authors: Graduate Institute of Clinical Medical Sciences, Chang-Gung University College of Medicine, Chang-Gung University, Taiwan.
authors: Gwo-Jyh
authors: GJ
authors: Chang
authors: Division of Nephrology, Department of Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.
authors: Yu-Juei
authors: YJ
authors: Hsu
authors: School of Dentistry, National Yang-Ming University, Taipei, Taiwan.
authors: Yuan-Min
authors: YM
authors: Lin
authors: Department of Biotechnology, Ming-Chuan University, Taoyuan, Taiwan.
authors: Yun-Shien
authors: YS
authors: Lee
authors: Cardiovascular Division, Chang-Gung Memorial Hospital, Chang-Gung University College of Medicine, Taoyuan, Taiwan.
authors: Chun-Li
authors: CL
authors: Wang
authors: Cardiovascular Division, Chang-Gung Memorial Hospital, Chang-Gung University College of Medicine, Taoyuan, Taiwan. Electronic address: yeongshinn@cgmh.org.tw.
authors: Yung-Hsin
authors: YH
authors: Yeh
mesh_terms: D000368:Aged; D001057:Apolipoproteins E / Q000235:genetics; D020517:Atrial Appendage / Q000473:pathology / Q000503:physiopathology; D001281:Atrial Fibrillation / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D064752:Atrial Remodeling / Q000235:genetics*; D020013:Calcium Signaling / Q000235:genetics*; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D006801:Humans; D008297:Male; D008875:Middle Aged; D058925:Receptors, Purinergic P2Y12 / Q000235:genetics; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics*; D013927:Thrombosis / Q000235:genetics*; D053773:Transforming Growth Factor beta1 / Q000235:genetics
chemical_list: C000612345:ApoE protein, human; D001057:Apolipoproteins E; C548576:P2RY12 protein, human; D058925:Receptors, Purinergic P2Y12; D053773:Transforming Growth Factor beta1; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; C506946:ATP2A2 protein, human
keywords: Atrial fibrillation; Atrium; Ion channel; Microarray