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

Abstract

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.

• Authors: Xuelian Li, GuoYuan Wang, MuGe QiLi, HaiHai Liang, TianShi Li, XiaoQiang E, Ying Feng, Ying Zhang, Xiao Liu, Ming Qian, BoZhi Xu, ZhiHang Shen, Samuel Chege Gitau, DanDan Zhao, HongLi Shan
• Journal: Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology (Cell Physiol Biochem) Vol. 45 Issue 5 Pg. 1955-1965 ( 2018) ISSN: 1421-9778 [Electronic] Germany
• PMID: 29518782 (Publication Type: Journal Article)
• Copyright: © 2018 The Author(s). Published by S. Karger AG, Basel.

Chemical References

• Actins
• Collagen Type I
• Serpin E2
• alpha-smooth muscle actin, mouse
• beta Catenin
• Angiotensin II
• Proto-Oncogene Proteins c-akt
• Mitogen-Activated Protein Kinase 1
• Mitogen-Activated Protein Kinase 3
• Aspirin

Topics

• Actins (metabolism)
• Angiotensin II (pharmacology)
• Animals
• Aspirin (pharmacology, therapeutic use)
• Cell Line
• Collagen Type I (metabolism)
• Disease Models, Animal
• Fibroblasts (cytology, drug effects, metabolism)
• Fibrosis
• Heart Failure (metabolism, pathology, prevention & control)
• Male
• Mice
• Mice, Inbred C57BL
• Mitogen-Activated Protein Kinase 1 (metabolism)
• Mitogen-Activated Protein Kinase 3 (metabolism)
• Myocardium (cytology)
• Phosphorylation (drug effects)
• Proto-Oncogene Proteins c-akt (metabolism)
• Serpin E2 (metabolism)
• Signal Transduction (drug effects)
• beta Catenin (metabolism)