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Matrine attenuates cardiac fibrosis by affecting ATF6 signaling pathway in diabetic cardiomyopathy.
Eur J Pharmacol. 2017 Jun 05; 804:21-30.EJ

Abstract

Cardiac function and compliance impairments are the features of cardiac fibrosis. Matrine shows therapeutic effects on cardiovascular diseases and organ fibrosis. In this study, we examined the therapeutic effects and mechanisms of matrine on cardiac fibrosis of DbCM. Matrine was administrated orally to rats with DbCM. Cardiac functions and compliance were evaluated. The collagen deposition was visualized by sirius red staining. Real-time PCR was used to determine the expression level of miRNA. Western blotting was performed to assess the protein expression. NFAT nuclear translocation was evaluated by fluorescent immunochemistry staining and Western blotting. Intracellular calcium level was assessed by fura-2/AM staining. A colorimetric method was used to determine calcineurin enzymatic activity. Impaired cardiac function and compliance were observed in rats with DbCM. Increased collagen deposition in cardiac tissue was found. Furthermore, ATF6 signaling was activated, leading to intracellular calcium accumulation and NFAT activation which further initiated ECM gene expressions. Matrine administration recovered cardiac function and improved compliance by exerting inhibitory effects against ATF6 signaling- induced fibrosis. The high- glucose incubation induced ATF6 signaling activation in cultured CFs to increase the synthesis of ECM. Matrine blocked the ATF6 signaling in CFs to inhibit ECM synthesis within non- cytotoxic concentrations. ATF6 signaling induced cardiac fibrosis was one of the mechanisms involved in DbCM, which was characterized by loss of cardiac compliance and functions. Matrine attenuated cardiac compliance and improved left ventricular functions by exerting therapeutic effects against cardiac fibrosis via affecting ATF6 signaling pathway.

Authors+Show Affiliations

Department of Cardiology, Shaanxi Provincial People's Hospital, Xi'an 710000, China; Institute of Molecular Genetics, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an 710000, China. Electronic address: liuzhongwei@xjtu.edu.cn.Department of Cardiology, Shaanxi Provincial People's Hospital, Xi'an 710000, China. Electronic address: zhangyong971292@163.com.Department of Cardiology, Shaanxi Provincial People's Hospital, Xi'an 710000, China. Electronic address: keplbr@sina.com.Department of Cardiology, Shaanxi Provincial People's Hospital, Xi'an 710000, China. Electronic address: hhjadk@sina.com.Department of Cardiology, Shaanxi Provincial People's Hospital, Xi'an 710000, China. Electronic address: mzjwoy@sina.com.Department of Cardiology, Shaanxi Provincial People's Hospital, Xi'an 710000, China. Electronic address: parker1985@163.com.Department of Biostatistics & Bioinformatics, School of Public Health & Tropical Medicine, Tulane University, New Orleans 70112, USA. Electronic address: qcshare@gmail.com.Department of Cardiology, Shaanxi Provincial People's Hospital, Xi'an 710000, China. Electronic address: gongchang_guan@sina.com.Department of Cardiology, Shaanxi Provincial People's Hospital, Xi'an 710000, China. Electronic address: junkuiwang@yeah.net.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

28373137

Citation

Liu, Zhongwei, et al. "Matrine Attenuates Cardiac Fibrosis By Affecting ATF6 Signaling Pathway in Diabetic Cardiomyopathy." European Journal of Pharmacology, vol. 804, 2017, pp. 21-30.
Liu Z, Zhang Y, Tang Z, et al. Matrine attenuates cardiac fibrosis by affecting ATF6 signaling pathway in diabetic cardiomyopathy. Eur J Pharmacol. 2017;804:21-30.
Liu, Z., Zhang, Y., Tang, Z., Xu, J., Ma, M., Pan, S., Qiu, C., Guan, G., & Wang, J. (2017). Matrine attenuates cardiac fibrosis by affecting ATF6 signaling pathway in diabetic cardiomyopathy. European Journal of Pharmacology, 804, 21-30. https://doi.org/10.1016/j.ejphar.2017.03.061
Liu Z, et al. Matrine Attenuates Cardiac Fibrosis By Affecting ATF6 Signaling Pathway in Diabetic Cardiomyopathy. Eur J Pharmacol. 2017 Jun 5;804:21-30. PubMed PMID: 28373137.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Matrine attenuates cardiac fibrosis by affecting ATF6 signaling pathway in diabetic cardiomyopathy. AU - Liu,Zhongwei, AU - Zhang,Yong, AU - Tang,Zhiguo, AU - Xu,Jing, AU - Ma,Meijuan, AU - Pan,Shuo, AU - Qiu,Chuan, AU - Guan,Gongchang, AU - Wang,Junkui, Y1 - 2017/03/31/ PY - 2017/02/06/received PY - 2017/03/27/revised PY - 2017/03/30/accepted PY - 2017/4/5/pubmed PY - 2017/11/11/medline PY - 2017/4/5/entrez KW - ATF6 KW - Calcineurin KW - Calcium KW - Calreticulin KW - Cardiac fibroblasts KW - Diabetic cardiomyopathy KW - Fibrosis KW - Matrine SP - 21 EP - 30 JF - European journal of pharmacology JO - Eur J Pharmacol VL - 804 N2 - Cardiac function and compliance impairments are the features of cardiac fibrosis. Matrine shows therapeutic effects on cardiovascular diseases and organ fibrosis. In this study, we examined the therapeutic effects and mechanisms of matrine on cardiac fibrosis of DbCM. Matrine was administrated orally to rats with DbCM. Cardiac functions and compliance were evaluated. The collagen deposition was visualized by sirius red staining. Real-time PCR was used to determine the expression level of miRNA. Western blotting was performed to assess the protein expression. NFAT nuclear translocation was evaluated by fluorescent immunochemistry staining and Western blotting. Intracellular calcium level was assessed by fura-2/AM staining. A colorimetric method was used to determine calcineurin enzymatic activity. Impaired cardiac function and compliance were observed in rats with DbCM. Increased collagen deposition in cardiac tissue was found. Furthermore, ATF6 signaling was activated, leading to intracellular calcium accumulation and NFAT activation which further initiated ECM gene expressions. Matrine administration recovered cardiac function and improved compliance by exerting inhibitory effects against ATF6 signaling- induced fibrosis. The high- glucose incubation induced ATF6 signaling activation in cultured CFs to increase the synthesis of ECM. Matrine blocked the ATF6 signaling in CFs to inhibit ECM synthesis within non- cytotoxic concentrations. ATF6 signaling induced cardiac fibrosis was one of the mechanisms involved in DbCM, which was characterized by loss of cardiac compliance and functions. Matrine attenuated cardiac compliance and improved left ventricular functions by exerting therapeutic effects against cardiac fibrosis via affecting ATF6 signaling pathway. SN - 1879-0712 UR - https://www.unboundmedicine.com/medline/citation/28373137/Matrine_attenuates_cardiac_fibrosis_by_affecting_ATF6_signaling_pathway_in_diabetic_cardiomyopathy_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0014-2999(17)30230-3 DB - PRIME DP - Unbound Medicine ER -