Intracardiac extracellular vesicle release in post-infarction diabetic hearts

Abstract

Introduction Cardiovascular disease (CVD) is the main cause of death in non-communicable diseases. In response to myocardial infarction (MI), extracellular vesicles (EVs) including large (lEVs) and small (sEVs), are released within and from the heart to facilitate intercellular communication and maintaining cardiac homeostasis. Objective As diabetes increases the risk of CVD, the purpose of the study was to investigate how diabetes influences the release of intracardiac EVs after MI. Method C57BL/6\xa0J male mice were fed normal chow diet or high-fat diet (HFD) for 3 months. HFD fed mice were glucose intolerant as attested by the measure of GTT above 200 mg/mL. Mice were subjected to MI by permanent ligation of the left anterior descending artery and sham animals underwent similar surgical procedure without ligation. Left ventricles from sham or MI mice were then harvested at either 15, 24, 48 or 72\xa0hours after surgery (N\xa0=\xa05 per group at each time point) and processed for EV extraction by differential centrifugation. EVs were quantified and analyzed via Tunable Resistive Pulse Sensing Technology (TRPS), flow cytometry and Western blot. Results In chow diet fed mice, release of both lEVs and sEVs was increased at 24\xa0h post-MI when compared to shams. These findings were in agreement with previous data obtained in younger control animals. In diabetic mice, lEVs peaked at 24\xa0h post-MI and this increase was slightly greater than that observed in chow diet fed mice. However, there were no differences in sEV release between sham and MI diabetic mice. TRPS analysis revealed that diabetes does not change EV size and population. Furthermore, both control and diabetic derived EVs harboured cardiomyocyte marker (Troponin\xa0T) as revealed by Western blot. Conclusion Our results show that diabetes modulates the release of both intracardiac sEVs and lEVs after MI. Further work will be needed to fully investigate the functional impact of cardiac EVs in the diabetic heart after MI.