Protecting cardiomyocytes from hypoxia-reoxygenation injury, empaglifozin and liraglutide alone or in combination?-Reference-Cited by-同舟云学术

Protecting cardiomyocytes from hypoxia-reoxygenation injury, empaglifozin and liraglutide alone or in combination?

Published:2024-01-01 Issue:1-2 Volume:35 Page:53-60
ISSN:2191-0286
Container-title:Journal of Basic and Clinical Physiology and Pharmacology
language:en
Short-container-title:

Author:

Amici Francesca¹,Ciarlo Christian¹,Abumusallam Jenine¹,Kravitz Madeline¹,Weber Angel-Rose¹,Meister Hanna¹,Li Zhao²^ORCID

Affiliation:

1. School of Pharmacy and Physician Assistant Studies , 8515 University of Saint Joseph , West Hartford , CT , USA

2. Department of Pharmaceutical Sciences , 8515 University of Saint Joseph , West Hartford , CT , USA

Abstract

Abstract Objectives Empagliflozin, a sodium-dependent glucose co-transporter 2 (SGLT2) inhibitor, and liraglutide, a GLP-1 receptor (GLP-1R) agonist, are commonly recognized for their cardiovascular benefits in individuals with type 2 diabetes (T2D). In prior studies, we have demonstrated that both drugs, alone or in combination, were able to protect cardiomyocytes from injury induced by diabetes. Mechanistic investigations also suggested that the cardioprotective effect may be independent of diabetes In this study, we utilized a hypoxia-reoxygenation (H/R) model to investigate the cardiovascular benefits of SGLT2 inhibitor empagliflozin and GLP-1 receptor (GLP-1R) agonist liraglutide, both alone and in combination, in the absence of T2D. Our hypothesis was that empagliflozin and liraglutide, either individually or in combination, would demonstrate cardioprotective properties against H/R-induced injury, with an additive and/or synergistic effect anticipated from combination therapy. Methods In this study, the cardiac muscle cell line, HL-1 cells, were treated with vehicle, empagliflozin, liraglutide, or a combination of the two drugs. The cells were then subjected to a hypoxia-reoxygenation (H/R) protocol, consisting of 1 h of hypoxia followed by 24 h of reoxygenation. The effects of the treatments on cytotoxicity, oxidative stress, endothelial nitric oxide synthase (eNOS) activity, phospho-protein kinase C (PKC) beta and phospho-eNOS (Thr495) expression were subsequently evaluated at the end of the treatments. Results We found that H/R increased cytotoxicity and reduces eNOS activity, empagliflozin, liraglutide or combination treatment attenuated some or all of these effects with the combination therapy showing the greatest improvement. Conclusions Empagliflozin, liraglutide or combination of these two have cardioprotective effect regardless of diabetes. Cardioprotective effects of SGLT2 inhibitor and GLP-1R agonist is additive and synergistic.

Publisher

Walter de Gruyter GmbH

Link

https://www.degruyter.com/document/doi/10.1515/jbcpp-2023-0029/pdf

Reference17 articles.

1. Lehrke, M, Marx, N. Diabetes mellitus and heart failure. Am J Cardiol 2017;120:S37–S47. https://doi.org/10.1016/j.amjcard.2017.05.014.

2. American Diabetes Association. Standards of medical care in diabetes 2019;42:21.

3. Verma, S, Rawat, S, Ho, KL, Wagg, CS, Zhang, L, Teoh, H, et al.. Empagliflozin increases cardiac energy production in diabetes: novel translational insights into the heart failure benefits of SGLT2 inhibitors. JACC Basic Transl Sci 2018;3:575–87. https://doi.org/10.1016/j.jacbts.2018.07.006.

4. Marso, SP, Daniels, GH, Brown-Frandsen, K, Kristensen, P, Mann, JF, Nauck, MA, et al.. Liraglutide and cardiovascular outcomes in type 2 diabetes. N Engl J Med 2016;375:311–22. https://doi.org/10.1056/nejmoa1603827.

5. Abdul-Ghani, M, Del Prato, S, Chilton, R, DeFronzo, RA. SGLT2 inhibitors and cardiovascular risk: lessons learned from the EMPA-REG OUTCOME study. Diabetes Care 2016;39:717–25. https://doi.org/10.2337/dc16-0041.