PMID- 25955429 OWN - NLM STAT- MEDLINE DCOM- 20160324 LR - 20200213 IS - 1791-244X (Electronic) IS - 1107-3756 (Print) IS - 1107-3756 (Linking) VI - 36 IP - 1 DP - 2015 Jul TI - Interleukin-17A contributes to the development of post-operative atrial fibrillation by regulating inflammation and fibrosis in rats with sterile pericarditis. PG - 83-92 LID - 10.3892/ijmm.2015.2204 [doi] AB - Post-operative atrial fibrillation (AF) remains a common cause of morbidity. Increasing evidence indicates that inflammation and atrial fibrosis contribute to the pathogenesis of this condition. Interleukin (IL)-17A, a potent pro-inflammatory cytokine, has been implicated in the development of a number of cardiovascular diseases. However, its role in post-operative AF remains unknown. In the present study, sterile pericarditis (SP) was induced in rats by the epicardial application of sterile talc. AF was induced by transesophageal burst pacing. Western blot analysis was applied to quantify the expression of IL-17A. Quantitative PCR was used to detect the mRNA expression of IL-17A, IL-6, IL-1beta, transforming growth factor-beta1 (TGF-beta1), collagen type 1 (Col-1), collagen type 3 (Col-3) and alpha-smooth muscle actin (alpha-SMA). Gelatin zymography and reverse gelatin zymography were used to quantify the levels of matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs (TIMPs). Histological analyses were performed to determine the extent of tissue inflammation and fibrosis. The rats with SP presented with a shorter refractoriness, a higher incidence and duration of AF, an enhanced susceptibility to developing AF, increased mRNA levels of AF-related pro-inflammatory cytokines (IL-6, IL-1beta and TGF-beta1), as well as marked atrial inflammation and fibrosis. The atrial IL-17A levels were elevated and correlated with the probability of developing AF. Treatment with anti-IL-17A monoclonal antibody decreased the levels of atrial IL-17A, prolonged refraction and markedly suppressed the development of AF. Simultaneously, inflammation and fibrosis were alleviated, which was further demonstrated by a decreased expression of AF-related pro-inflammatory cytokines, a downregulation in fibrosis-related mRNA expression (Col-1, Col-3 and alpha-SMA) and by the decreased activity of MMP-2/9 and TIMPs. Thus, the findings of our study indicate that IL-17A may play a pathogenic role in post-operative AF by inducing inflammation and fibrosis in rats with SP. FAU - Fu, Xiao-Xing AU - Fu XX AD - Research Center of Ion Channelopathy, Institute of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China. FAU - Zhao, Ning AU - Zhao N AD - Research Center of Ion Channelopathy, Institute of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China. FAU - Dong, Qian AU - Dong Q AD - Research Center of Ion Channelopathy, Institute of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China. FAU - Du, Li-Li AU - Du LL AD - Research Center of Ion Channelopathy, Institute of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China. FAU - Chen, Xiao-Jun AU - Chen XJ AD - Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350108, P.R. China. FAU - Wu, Qiong-Feng AU - Wu QF AD - Research Center of Ion Channelopathy, Institute of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China. FAU - Cheng, Xiang AU - Cheng X AD - Research Center of Ion Channelopathy, Institute of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China. FAU - Du, Yi-Mei AU - Du YM AD - Research Center of Ion Channelopathy, Institute of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China. FAU - Liao, Yu-Hua AU - Liao YH AD - Research Center of Ion Channelopathy, Institute of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20150508 PL - Greece TA - Int J Mol Med JT - International journal of molecular medicine JID - 9810955 RN - 0 (Actins) RN - 0 (Collagen Type I) RN - 0 (Collagen Type III) RN - 0 (IL1B protein, rat) RN - 0 (Il17a protein, rat) RN - 0 (Interleukin-17) RN - 0 (Interleukin-1beta) RN - 0 (Interleukin-6) RN - 0 (RNA, Messenger) RN - 0 (Tissue Inhibitor of Metalloproteinases) RN - 0 (Transforming Growth Factor beta1) RN - 0 (smooth muscle actin, rat) RN - 14807-96-6 (Talc) RN - EC 3.4.24.- (Matrix Metalloproteinases) SB - IM MH - Actins/genetics MH - Animals MH - Atrial Fibrillation/*pathology MH - Collagen Type I/genetics MH - Collagen Type III/genetics MH - Fibrosis/*immunology MH - Inflammation/*immunology MH - Interleukin-17/genetics/*immunology MH - Interleukin-1beta/genetics/metabolism MH - Interleukin-6/genetics/metabolism MH - Matrix Metalloproteinases/metabolism MH - Pericarditis/immunology/*pathology MH - RNA, Messenger/biosynthesis/genetics MH - Rats MH - Rats, Sprague-Dawley MH - Talc MH - Tissue Inhibitor of Metalloproteinases/metabolism MH - Transforming Growth Factor beta1/genetics/metabolism PMC - PMC4494571 EDAT- 2015/05/09 06:00 MHDA- 2016/03/25 06:00 PMCR- 2015/05/08 CRDT- 2015/05/09 06:00 PHST- 2014/10/18 00:00 [received] PHST- 2015/05/05 00:00 [accepted] PHST- 2015/05/09 06:00 [entrez] PHST- 2015/05/09 06:00 [pubmed] PHST- 2016/03/25 06:00 [medline] PHST- 2015/05/08 00:00 [pmc-release] AID - ijmm-36-01-0083 [pii] AID - 10.3892/ijmm.2015.2204 [doi] PST - ppublish SO - Int J Mol Med. 2015 Jul;36(1):83-92. doi: 10.3892/ijmm.2015.2204. Epub 2015 May 8.