Long-term aerobic exercise training in type two diabetic patients alters the expression of miRNA-223 and its corresponding target, the P2RY12 receptor, attenuating platelet function
Affiliations: [a]
Department of Exercise Physiology, Faculty of Sport Sciences, University of Isfahan, Isfahan, Iran
| [b]
Institute of Biotechnology, Molecular Cell Biology, Brandenburg University of Technology Cottbus-Senftenberg, Senftenberg, Germany
| [c]
Cell-Based Therapies Research Center, Digestive Disease Research Institute, Tehran University of Medical Sciences, Tehran, Iran
Correspondence:
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Corresponding author: Mehdi Kargarfard, Department of Exercise Physiology, Faculty of Sport Sciences, University of Isfahan, Isfahan 8174673441, Iran. Tel.: +983137934282; Fax: +983136687572; E-mail: m.kargarfard@spr.ui.ac.ir, ORCID ID: 0000-0002-9205-799X
Abstract: BACKGROUND:Type two diabetes mellitus (T2DM) patients are prone to develop atherothrombotic events due to platelet hyper-reactivity stemming from platelet miRNA-223 down-regulation and over-expression of its corresponding target, P2RY12. OBJECTIVE:The study sought to determine the effects of long-term aerobic training on the expression levels of miRNA-223 and P2RY12 mRNA, and platelet function in T2DM patients. METHODS:Twenty-four patients with T2DM (age, 60.0±2.8 yrs.) were selected and randomly divided into two groups: aerobic exercise training (AET, n = 12) and control (CON, n = 12). The AET protocol was performed with moderate intensity for 12 weeks, while patients in the CON group followed their usual routine. Weight, body mass index (BMI), peak oxygen consumption (VO2peak), lipid profile, fasting blood glucose (FBG), glycated hemoglobin (HbA1c), insulin resistance index (HOMA-IR), platelet miRNA-223 and P2RY12 expression were measured before and after the period. RESULTS:There was a significant improvement in body weight, BMI, VO2peak, FBG, HbA1c, and HOMA-IR, after 12 weeks of AET (P < 0.01). Platelet aggregation decreased significantly after 12 weeks in the AET group compared with the CON (P < 0.001) group. Platelets’ miRNA-223 and P2RY12 were significantly up- and down-regulated after AET in comparison with the CON group (P < 0.05), respectively. Moreover, the relative expression of miRNA-223 and P2RY12 significantly correlated with FBG changes following the intervention. CONCLUSIONS:It can be concluded that long-term moderate-intensity aerobic training might be effective for reducing the occurrence of atherothrombotic events leading to premature death in T2DM patients through the modulation of miRNA-223, P2RY12 receptor expression, and platelet function.
