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Myocardial Ischemia-Reperfusion and Diabetes: Lessons Learned From Bedside to Bench

Abstract : In front of the failure to translate from bench to bedside cardioprotective drugs against myocardial ischemia-reperfusion, research scientists are currently revising their animal models. Owing to its growing incidence nowadays, type 2 diabetes (T2D) represents one of the main risk factors of co-morbidities in myocardial infarction. However, discrepancies exist between reported animal and human studies. Our aim was here to compare the impact of diabetes on cell death after cardiac ischemia-reperfusion in a human cohort of ST-elevation myocardial infarction (STEMI) patients with a diet-induced mouse model of T2D, using a high-fat high-sucrose diet for 16 weeks (HFHSD). Interestingly, a small fraction (<14%) of patients undergoing a myocardial infarct were diabetic, but treated, and did not show a bigger infarct size when compared to non-diabetic patients. On the contrary, HFHSD mice displayed an increased infarct size after an in vivo cardiac ischemia-reperfusion, together with an increased cell death after an in vitro hypoxia-reoxygenation on isolated cardiomyocytes. To mimic the diabetic patients' medication profile, 6 weeks of oral gavage with Metformin was performed in the HFHSD mouse group. Metformin treatment of the HFHSD mice led to a similar extent of lower cell death after hypoxia-reoxygenation as in the standard diet group, compared to the HFHSD cardiomyocytes. Altogether, our data highlight that due to their potential protective effect, anti-diabetic medications should be included in pre-clinical study of cardioprotective approaches. Moreover, since diabetic patients represent only a minor fraction of the STEMI patients, diabetic animal models may not be the most suitable translatable model to humans, unlike aging that appears as a common feature of all infarcted patients.
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https://hal.inrae.fr/hal-03299392
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Submitted on : Monday, July 26, 2021 - 1:50:21 PM
Last modification on : Tuesday, August 24, 2021 - 4:22:29 PM

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Distributed under a Creative Commons Attribution 4.0 International License

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Maya Dia, Alexandre Paccalet, Bruno Pillot, Christelle Leon, Michel Ovize, et al.. Myocardial Ischemia-Reperfusion and Diabetes: Lessons Learned From Bedside to Bench. Frontiers in Cardiovascular Medicine, Frontiers Media, 2021, 8, ⟨10.3389/fcvm.2021.660698⟩. ⟨hal-03299392⟩

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