title: Eplerenone inhibits atrial fibrosis in mutant TGF-β1 transgenic mice.
abstract: The purpose of the present study was to study the impacts of eplerenone (EPL), an antagonist of mineralocorticoid receptors (MR), on atrial fibrosis in a mouse model with selective fibrosis in the atrium, and to explore the possible mechanisms. Using mutant TGF-β1 transgenic (Tx) mice, we first demonstrated that EPL inhibited atrial fibrosis specifically and decreased macrophage accumulation in the atria of these mice. Results from immunohistochemistry and western blotting showed that EPL attenuated protein expression of fibrosis-related molecules such as connective tissue growth factor (CTGF) and fibronectin in the atria of Tx mice. In culture, EPL inhibited gene expression of fibrosis-related molecules such as fibronectin, α-SMA, and CTGF in TGF-β1-stimulated atrial fibroblasts. Finally, using a co-culture system, we showed that TGF-β1-stimulated atrial fibroblasts induced migration of macrophages and this was blocked by EPL. EPL also blocked TGF-β1-induced gene expression of intedeukin-6 (IL-6) in atrial fibroblasts. Therefore, we conclude that EPL attenuated atrial fibrosis and macrophage infiltration in Tx mice. TGF-β1 and IL-6 were involved in the impacts of EPL on activation of atrial fibroblasts and interactions between fibroblasts and macrophages.
authors.affiliation: Department of Cardiology, Shanghai Chest Hospital, Shanghai Jiao tong University, Shanghai, 200030, China.
authors.forename: Xiaoqing
authors.initials: X
authors.lastname: Chen
authors.affiliation: Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, University of the Chinese Academy of Sciences, Shanghai, 200031, China.
authors.forename: Wuchang
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Cardiology, Shanghai Chest Hospital, Shanghai Jiao tong University, Shanghai, 200030, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Department of Cardiology, Shanghai Chest Hospital, Shanghai Jiao tong University, Shanghai, 200030, China.
authors.forename: Lili
authors.initials: L
authors.lastname: Du
authors.affiliation: Department of Cardiology, Shanghai Chest Hospital, Shanghai Jiao tong University, Shanghai, 200030, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Yi
authors.affiliation: Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, University of the Chinese Academy of Sciences, Shanghai, 200031, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Cardiology, Shanghai Chest Hospital, Shanghai Jiao tong University, Shanghai, 200030, China. xkliuxu@126.com.
authors.forename: Xu
authors.initials: X
authors.lastname: Liu
authors.affiliation: Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, University of the Chinese Academy of Sciences, Shanghai, 200031, China. szduan@sibs.ac.cn.
authors.forename: Shengzhong
authors.initials: S
authors.lastname: Duan
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002478:Cells, Cultured; D018920:Coculture Techniques; D055513:Connective Tissue Growth Factor / Q000235:genetics / Q000378:metabolism; D000077545:Eplerenone; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D005353:Fibronectins / Q000235:genetics / Q000378:metabolism; D005355:Fibrosis / Q000235:genetics / Q000517:prevention & control; D015870:Gene Expression / Q000187:drug effects; D006325:Heart Atria / Q000378:metabolism / Q000473:pathology; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008856:Microscopy, Fluorescence; D000451:Mineralocorticoid Receptor Antagonists / Q000494:pharmacology; D009154:Mutation; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013148:Spironolactone / Q000031:analogs & derivatives* / Q000494:pharmacology; D053773:Transforming Growth Factor beta1 / Q000235:genetics* / Q000378:metabolism / Q000494:pharmacology
chemical_list: D005353:Fibronectins; D015850:Interleukin-6; D000451:Mineralocorticoid Receptor Antagonists; D053773:Transforming Growth Factor beta1; D055513:Connective Tissue Growth Factor; D013148:Spironolactone; D000077545:Eplerenone
keywords: TGF-β1; atrial fibroblasts; atrial fibrosis; eplerenone; macrophages