Differential left-to-right atria gene expression ratio in human sinus rhythm and atrial fibrillation: Implications for arrhythmogenesis and thrombogenesis

详细信息    查看全文

• 作者：Feng-Chun Tsai^a ; ¹ ; Yen-Chen Lin^b ; ¹ ; Shang-Hung Chang^b ; Gwo-Jyh Chang^e ; Yu-Juei Hsu^f ; Yuan-Min Lin^c ; Yun-Shien Lee^d ; Chun-Li Wang^b ; Yung-Hsin Yeh^b ; ^{yeongshinn@cgmh.org.tw" class="auth_mail" title="E-mail the corresponding author}
• 关键词：AF ; atrial fibrillation ; ApoE ; apolipoprotein E ; CD36 ; cluster of differentiation 36 ; DHE ; dihydroethidium ; ESTs ; expressed sequence tag ; IPA ; Ingenuity Pathway Analysis ; IP3R1 ; inositol 1 ; 4 ; 5-trisphosphate receptor type 1 ; LA ; left atrium ; P2RY12 ; purinergic receptor P2Y ; G-Protein coupled ; 12 ; qPCR ; quantitative polymerase chain reaction ; RA ; right atrium ; RyR2 ; ryanodine receptor 2 ; ROS ; reactive oxidative species ; SERCA2 ; sarcoplasmic/endoplasmic reticulum calcium ATPase 2 ; SR ; sinus rhythm
• 刊名：International Journal of Cardiology
• 出版年：2016
• 出版时间：1 November 2016
• 年：2016
• 卷：222
• 期：Complete
• 页码：104-112
• 全文大小：1382 K

文摘

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.