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

• Published in: Frontiers in cardiovascular medicine Vol. 8; p. 660698
• Main Authors: Dia, Maya, Paccalet, Alexandre, Pillot, Bruno, Leon, Christelle, Ovize, Michel, Crola Da Silva, Claire, Bochaton, Thomas, Paillard, Melanie
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media 26.03.2021; Frontiers Media S.A
• Subjects: animal model; Cardiology and cardiovascular system; Cardiovascular Medicine; diabetes mellitus; human; Human health and pathology; Life Sciences; medication; myocardia infarction; diabetes mellitus; medication; myocardia infarction; animal model; human
• ISSN: 2297-055X; 2297-055X
• DOI: 10.3389/fcvm.2021.660698

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 cardiac ischemia-reperfusion, together with an increased cell death after an 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.