Protecting cardiomyocytes from hypoxia-reoxygenation injury, empaglifozin and liraglutide alone or in combination?
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Francesca Amici
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.
Acknowledgments
This project is supported by student grants from the University of Saint Joseph to Francesca Amici, Christian Ciarlo and Jenine Abumusallam as well as TLCC grant from University of Saint Joseph to Dr. Zhao Li. I have no conflict of interest to disclose. I give the permission to reproduce material from other sources.
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Research ethics: The local Institutional Review Board deemed the study exempt from review.
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Informed consent: Informed consent was obtained from all individuals included in this study.
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Author contributions: The authors have accepted responsibility for the entire content of this manuscript and approved its submission.
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Competing interests: The authors state no conflict of interest.
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Research funding: This research is funded by research grant from TLC (teaching and learning center) of University of Saint Joseph.
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Data availability: The raw data can be obtained on request from the corresponding author.
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Artikel in diesem Heft
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Artikel in diesem Heft
- Frontmatter
- Editorials
- Can small molecule GLP-1 agonists be the next first-line drugs in type-2 diabetes mellitus?
- From Dr. Google to CE-marked medical devices: need for ethical and legal safeguards
- Minireview
- Antioxidant therapy for hepatic diseases: a double-edged sword
- Reviews
- Effect of cannabinoids in mild-to-moderate cases of Crohn’s disease as compared to placebo: a systematic review and meta-analysis of randomised controlled trials
- Evidences and therapeutic advantages of donanemab in the treatment of early Alzheimer’s disease
- Alzheimer’s disease and clinical trials
- Original Articles
- Pioglitazone attenuate level of myeloperoxidases and nitic oxide in psoriatic lesion: a proof-of-concept study in a imiquimod induced psoriasis model in rat
- Protecting cardiomyocytes from hypoxia-reoxygenation injury, empaglifozin and liraglutide alone or in combination?
- Gasotransmitters do not prevent changes in transepithelial ion transport induced by hypoxia followed by reoxygenation
- High-intensity combination exercise has the highest effect on increasing serum irisin and interleukin 6 levels in women with obesity
- Impact of heat stress on thermal balance, hydration and cortical response among outdoor workers in hot environment – an exploratory report from North East India
- Maternal separation influences hepatic drug-metabolizing CYP450 gene expression without pathological changes in adult mice
- Case Report
- Preoperative CT diagnosis of perforated Meckel’s diverticulitis in a young patient: a case report
