caa a22 4500 606236090 CHVBK 20210128101246.0 cr unu---uuuuu 210128e20150801xx s 000 0 eng 10.1007/s11010-015-2431-1 doi (NATIONALLICENCE)springer-10.1007/s11010-015-2431-1 TGF-β1 and TIMP-4 regulate atrial fibrosis in atrial fibrillation secondary to rheumatic heart disease [Elektronische Daten] [Yu Sun, Zi-Yang Huang, Zhen-Hua Wang, Cui-Ping Li, Xian-Liang Meng, Yun-Jiao Zhang, Feng Su, Nan Ma] To investigate the involvement of transforming growth factor-β1 (TGF-β1) and tissue inhibitor of metalloproteinase 4 (TIMP-4) in influencing the severity of atrial fibrosis in rheumatic heart disease (RHD) patients with atrial fibrillation (AF). The degree of myocardial fibrosis was evaluated using Masson staining. The expression levels of TGF-β1, TIMP-4, matrix metalloproteinase-2 (MMP-2), type I collagen, and type III collagen were estimated by Western blot analysis. Additionally, TGF-β1 and TIMP-4 mRNA levels were quantified by qRT-PCR. The effect of TGF-β1 stimulation on TIMP-4 expression was assessed by in vitro stimulation of freshly isolated human atrial fibroblasts with recombinant human TGF-β1, followed by Western blot analysis to detect changes in TIMP-4 levels. Masson stain revealed that the left atrial diameter and collagen volume fraction were obviously increased in AF patients, compared to sinus rhythm (SR) controls (both P<0.05). Western blot analysis showed significantly elevated levels of the AF markers MMP-2, type I collagen, and type III collagen in the AF group, in comparison to the SR controls (all P<0.05). In the AF group, TGF-β1 expression was relatively higher, while TIMP-4 expression was apparently lower than the SR group (all P<0.05). TIMP-4 expression level showed a negative association with TGF-β1 expression level (r=−0.98, P<0.01) and TGF-β1 stimulation of atrial fibroblasts led to a sharp decrease in TIMP-4 protein level. Increased TGF-β1 expression and decreased TIMP-4 expression correlated with atrial fibrosis and ECM changes in the atria of RHD patients with AF. Notably, TGF-β1 suppressed TIMP-4 expression, suggesting that selective TGF-β1 inhibitors may be useful therapeutic agents. Springer Science+Business Media New York, 2015 Atrial fibrillation nationallicence Atrial fibrosis nationallicence Rheumatic heart disease nationallicence Tissue inhibitor metalloproteinase 4 nationallicence Transforming growth factor-β1 nationallicence Matrix metalloproteinase-2 nationallicence Sun Yu Cardiovascular Department, Second Affiliated Hospital and Second Clinical Medical College, Fujian Medical University, Zhongshan North Road No.34, 362000, Quanzhou, Fujian Province, People's Republic of China aut Huang Zi-Yang Cardiovascular Department, Second Affiliated Hospital and Second Clinical Medical College, Fujian Medical University, Zhongshan North Road No.34, 362000, Quanzhou, Fujian Province, People's Republic of China aut Wang Zhen-Hua Cardiovascular Department, Second Affiliated Hospital and Second Clinical Medical College, Fujian Medical University, Zhongshan North Road No.34, 362000, Quanzhou, Fujian Province, People's Republic of China aut Li Cui-Ping Binzhou City Center Hospital, 251700, Binzhou, Shandong Province, People's Republic of China aut Meng Xian-Liang Binzhou City Center Hospital, 251700, Binzhou, Shandong Province, People's Republic of China aut Zhang Yun-Jiao Cardiovascular Department, Second Affiliated Hospital and Second Clinical Medical College, Fujian Medical University, Zhongshan North Road No.34, 362000, Quanzhou, Fujian Province, People's Republic of China aut Su Feng Cardiovascular Department, Second Affiliated Hospital and Second Clinical Medical College, Fujian Medical University, Zhongshan North Road No.34, 362000, Quanzhou, Fujian Province, People's Republic of China aut Ma Nan Cardiovascular Department, Second Affiliated Hospital and Second Clinical Medical College, Fujian Medical University, Zhongshan North Road No.34, 362000, Quanzhou, Fujian Province, People's Republic of China aut Molecular and Cellular Biochemistry Springer US; http://www.springer-ny.com 406/1-2(2015-08-01), 131-138 0300-8177 406:1-2<131 2015 406 11010 https://doi.org/10.1007/s11010-015-2431-1 text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s11010-015-2431-1 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Sun Yu Cardiovascular Department, Second Affiliated Hospital and Second Clinical Medical College, Fujian Medical University, Zhongshan North Road No.34, 362000, Quanzhou, Fujian Province, People's Republic of China aut NATIONALLICENCE 700 1- Huang Zi-Yang Cardiovascular Department, Second Affiliated Hospital and Second Clinical Medical College, Fujian Medical University, Zhongshan North Road No.34, 362000, Quanzhou, Fujian Province, People's Republic of China aut NATIONALLICENCE 700 1- Wang Zhen-Hua Cardiovascular Department, Second Affiliated Hospital and Second Clinical Medical College, Fujian Medical University, Zhongshan North Road No.34, 362000, Quanzhou, Fujian Province, People's Republic of China aut NATIONALLICENCE 700 1- Li Cui-Ping Binzhou City Center Hospital, 251700, Binzhou, Shandong Province, People's Republic of China aut NATIONALLICENCE 700 1- Meng Xian-Liang Binzhou City Center Hospital, 251700, Binzhou, Shandong Province, People's Republic of China aut NATIONALLICENCE 700 1- Zhang Yun-Jiao Cardiovascular Department, Second Affiliated Hospital and Second Clinical Medical College, Fujian Medical University, Zhongshan North Road No.34, 362000, Quanzhou, Fujian Province, People's Republic of China aut NATIONALLICENCE 700 1- Su Feng Cardiovascular Department, Second Affiliated Hospital and Second Clinical Medical College, Fujian Medical University, Zhongshan North Road No.34, 362000, Quanzhou, Fujian Province, People's Republic of China aut NATIONALLICENCE 700 1- Ma Nan Cardiovascular Department, Second Affiliated Hospital and Second Clinical Medical College, Fujian Medical University, Zhongshan North Road No.34, 362000, Quanzhou, Fujian Province, People's Republic of China aut NATIONALLICENCE 773 0- Molecular and Cellular Biochemistry Springer US; http://www.springer-ny.com 406/1-2(2015-08-01), 131-138 0300-8177 406:1-2<131 2015 406 11010