Aspirin Reduces Cardiac Interstitial Fibrosis by Inhibiting Erk1/2-Serpine2 and P-Akt Signalling Pathways

• Published in: Cellular physiology and biochemistry Vol. 45; no. 5; pp. 1955 - 1965
• Main Authors: Li, Xuelian, Wang, GuoYuan, QiLi, MuGe, Liang, HaiHai, Li, TianShi, E, XiaoQiang, Feng, Ying, Zhang, Ying, Liu, Xiao, Qian, Ming, Xu, BoZhi, Shen, ZhiHang, Gitau, Samuel Chege, Zhao, DanDan, Shan, HongLi
• Format: Journal Article
• Language: English
• Published: Basel, Switzerland S. Karger AG 01.03.2018; Cell Physiol Biochem Press GmbH & Co KG
• Subjects: Actins - metabolism; Akt; Angiotensin II - pharmacology; Animals; Aspirin; Aspirin - pharmacology; Aspirin - therapeutic use; beta Catenin - metabolism; Blood platelets; Cancer; Cardiac Fibrosis; Cardiovascular disease; Cell Line; Collagen; Collagen Type I - metabolism; Disease Models, Animal; Disease prevention; Erk1/2; Fibroblasts; Fibroblasts - cytology; Fibroblasts - drug effects; Fibroblasts - metabolism; Fibrosis; Growth factors; Heart Failure - metabolism; Heart Failure - pathology; Heart Failure - prevention & control; Kinases; Laboratory animals; Male; Mice; Mice, Inbred C57BL; Mitogen-Activated Protein Kinase 1 - metabolism; Mitogen-Activated Protein Kinase 3 - metabolism; Myocardium - cytology; Original Paper; Phosphorylation - drug effects; Proto-Oncogene Proteins c-akt - metabolism; Rodents; Serpin E2 - metabolism; SerpinE2; Signal Transduction - drug effects; Thrombosis; United States > US; Erk1/2; SerpinE2; Aspirin; Akt; Cardiac Fibrosis
• ISSN: 1015-8987; 1421-9778
• DOI: 10.1159/000487972

Background/Aims: Cardiac interstitial fibrosis is an abnormality of various cardiovascular diseases, including myocardial infarction, hypertrophy, and atrial fibrillation, and it can ultimately lead to heart failure. However, there is a lack of practical therapeutic approaches to treat fibrosis and reverse the damage to the heart. The purpose of this study was to investigate the effect of long-term aspirin administration on pressure overload–induced cardiac fibrosis in mice and reveal the underlying mechanisms of aspirin treatment. Methods: C57BL/6 mice were subjected to transverse aortic constriction (TAC), and treated with 10 mg·kg -1 ·day -1 of aspirin for 4 weeks. Masson staining and a collagen content assay were used to detect the effects of aspirin on cardiac fibrosis in vivo and in vitro. Western blot and qRT-PCR were applied to examine the impact of aspirin on extracellular signal-regulated kinases (Erks), p-Akt/β-catenin, SerpinE2, collagen I, and collagen III levels in the mice heart. Results: Aspirin significantly suppressed the expression of α-smooth muscle actin (α-SMA; 1.19±0.19-fold) and collagen I (0.95±0.09-fold) in TAC mice. Aspirin, at doses of 100 and 1000 µM, also significantly suppressed angiotensin II-induced α-SMA and collagen I in cultured CFs. The enhanced phosphorylation of Erk1/2 caused by TAC (p-Erk1, 1.49±0.19-fold; p-Erk2, 1.96±0.68-fold) was suppressed by aspirin (p-Erk1, 1.04±0.15-fold; p-Erk2, 0.87±0.06-fold). SerpinE2 levels were suppressed via the Erk1/2 signalling pathway following treatment with aspirin (1.36±0.12-fold for TAC; 1.06±0.07-fold for aspirin+TAC). The p-Akt and β-catenin levels were also significantly inhibited in vivo and in vitro. Conclusions: Our study reveals a novel mechanism by which aspirin alleviates pressure overload-induced cardiac interstitial fibrosis in TAC mice by suppressing the p-Erk1/2 and p-Akt/β-catenin signalling pathways.