Haoliang Sun1, Junjie Zhang2, Yongfeng Shao1. 1. Department of Cardiovascular Surgery, the First Affiliated Hospital of Nanjing Medical University; Jiangsu-China. 2. Department of Cardiothoracic Surgery, Changzhou Wujin People's Hospital; Jiangsu-China.
Abstract
OBJECTIVE: This study aimed to investigate the functions of mRNA, long non-coding RNA (lncRNA), and circular RNA (circRNA) in paroxysmal and persistent atrial fibrillation (AF) patients. METHODS: A total of 9 left atrial appendage (LAA) tissues were collected from patients with AF (ParoAF patients = 3 and PersAF patients = 3) and donors (n=3). Genes and circRNAs were identified by per kilobase per million reads (RPKM) and number of circular reads/number of mapped reads/read length (SRPBM), respectively. Differentially expressed mRNAs (DE mRNAs), lncRNAs (DE lncRNAs), and circRNAs (DE circRNAs) were identified by | log2 (Fold Change) | ≥ 2 and p-value < 0.05. Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed. Protein-protein, mRNA-lncRNA, and circRNA-miRNA interaction networks were constructed. In addition, logistic analysis was conducted among AF and circRNAs. RESULTS: A total of 285 (116 up-regulated and 169 down-regulated) and 275 (110 up-regulated and 165 down-regulated) DE mRNAs, 575 (276 up-regulated and 299 down-regulated) and 583 (330 up-regulated and 253 down-regulated) DE lncRNAs, and 83 (48 up-regulated and 35 down-regulated) and 99 (58 up-regulated and 41 down-regulated) circRNAs were detected in ParoAF and PersAF, respectively, as compared with control. MAPK signal pathway as well as voltage-dependent, L type, and alpha 1C subunit calcium channel (CACNA1C) might participate in AF occurrence by preventing atrial parasympathetic remodeling. Collagen type I alpha 1 (COL1A1) and COL1A2 mostly participated in the enriched GO and KEGG terms and connected with most of the DE mRNAs. The expression of chr10: 69902697|69948883 was a protective factor against PersAF after adjusting for age (p=0.022, 95% CI: 0.003-0.634). CONCLUSION: We found that some mRNAs, lncRNAs, circRNAs, and pathways play essential roles in AF pathogenesis and development. Moreover, one protective factor against PersAF was detected.
OBJECTIVE: This study aimed to investigate the functions of mRNA, long non-coding RNA (lncRNA), and circular RNA (circRNA) in paroxysmal and persistent atrial fibrillation (AF) patients. METHODS: A total of 9 left atrial appendage (LAA) tissues were collected from patients with AF (ParoAF patients = 3 and PersAF patients = 3) and donors (n=3). Genes and circRNAs were identified by per kilobase per million reads (RPKM) and number of circular reads/number of mapped reads/read length (SRPBM), respectively. Differentially expressed mRNAs (DE mRNAs), lncRNAs (DE lncRNAs), and circRNAs (DE circRNAs) were identified by | log2 (Fold Change) | ≥ 2 and p-value < 0.05. Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed. Protein-protein, mRNA-lncRNA, and circRNA-miRNA interaction networks were constructed. In addition, logistic analysis was conducted among AF and circRNAs. RESULTS: A total of 285 (116 up-regulated and 169 down-regulated) and 275 (110 up-regulated and 165 down-regulated) DE mRNAs, 575 (276 up-regulated and 299 down-regulated) and 583 (330 up-regulated and 253 down-regulated) DE lncRNAs, and 83 (48 up-regulated and 35 down-regulated) and 99 (58 up-regulated and 41 down-regulated) circRNAs were detected in ParoAF and PersAF, respectively, as compared with control. MAPK signal pathway as well as voltage-dependent, L type, and alpha 1C subunit calcium channel (CACNA1C) might participate in AF occurrence by preventing atrial parasympathetic remodeling. Collagen type I alpha 1 (COL1A1) and COL1A2 mostly participated in the enriched GO and KEGG terms and connected with most of the DE mRNAs. The expression of chr10: 69902697|69948883 was a protective factor against PersAF after adjusting for age (p=0.022, 95% CI: 0.003-0.634). CONCLUSION: We found that some mRNAs, lncRNAs, circRNAs, and pathways play essential roles in AF pathogenesis and development. Moreover, one protective factor against PersAF was detected.
Authors: Moritz F Sinner; Nathan R Tucker; Kathryn L Lunetta; Kouichi Ozaki; J Gustav Smith; Stella Trompet; Joshua C Bis; Honghuang Lin; Mina K Chung; Jonas B Nielsen; Steven A Lubitz; Bouwe P Krijthe; Jared W Magnani; Jiangchuan Ye; Michael H Gollob; Tatsuhiko Tsunoda; Martina Müller-Nurasyid; Peter Lichtner; Annette Peters; Elena Dolmatova; Michiaki Kubo; Jonathan D Smith; Bruce M Psaty; Nicholas L Smith; J Wouter Jukema; Daniel I Chasman; Christine M Albert; Yusuke Ebana; Tetsushi Furukawa; Peter W Macfarlane; Tamara B Harris; Dawood Darbar; Marcus Dörr; Anders G Holst; Jesper H Svendsen; Albert Hofman; Andre G Uitterlinden; Vilmundur Gudnason; Mitsuaki Isobe; Rainer Malik; Martin Dichgans; Jonathan Rosand; David R Van Wagoner; Emelia J Benjamin; David J Milan; Olle Melander; Susan R Heckbert; Ian Ford; Yongmei Liu; John Barnard; Morten S Olesen; Bruno H C Stricker; Toshihiro Tanaka; Stefan Kääb; Patrick T Ellinor Journal: Circulation Date: 2014-08-14 Impact factor: 29.690