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

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.

Epigenetic regulation of aging: implications for interventions of aging and diseases

“… 375 , 377 , 378 Exercise also modulates the microRNA expression profile (such as miR-423-3p, miR-451a, miR-766-3p, miR-130a, and miRNA-223) in subjects with type 2 diabetes, which may be involved in the improvement of weight loss, blood glucose control, and insulin sensitivity. 379 – 381 In addition, the combination of diet and lifestyle interventions, including exercise, sleep, relaxation guidance, supplemental probiotics and phytonutrients, reverses the epigenetic age in healthy adult males. 362 …”

Impact of Physical Exercise on Platelets: Focus on Its Effects in Metabolic Chronic Diseases

“…The studies reviewed included the effects of both short-term strenuous and long-term exercise on platelet function and activation. The majority of studies, independently of type of metabolic disorder, indicated the beneficial effect of prolonged moderate-intensity training exercise on platelets in terms of aggregation and activation [ 75 , 135 , 189 , 226 , 246 , 247 , 249 ]. The effects of acute strenuous exercise on platelet response were contradictory.…”

“…Specifically, aerobic training for 8 weeks determines a remarkable reduction in MPV, PDW, and collagen-induced platelet aggregation [ 246 ], attributable at least in part to downregulated glycoprotein (GP)IIb expression. A 12-week moderate-intensity aerobic exercise program was effective in upregulating platelets’ microRNAs (miRNA)-223 and downregulating P2RY12 receptor expression following decreased platelet aggregability in T2DM patients [ 247 ], whereas short-term endurance training determined a positive impact on platelet function, glycemic indices, physical fitness, and body composition, but did not change miRNA-223 levels and P2RY12 expression [ 248 ]. One year of exercise training was not effective in modifying platelet-derived microvesicles in T2DM patients with CAD, but decreased levels of PMVs carrying TF [CD61 + /CD142 + /Annexin V (AV) + ] and von Willebrand factor (vWF; CD31 + /CD42b + /AV + ) in those with albuminuria [ 249 ].…”

Exercise, Spinal Microglia and Neuropathic Pain: Potential Molecular Mechanisms

“…However, low- and high-intensity exercise instead increased the expression of P2X7R [ 54 ]. Another study has shown that long-term moderate-intensity aerobic training may effectively reduce the occurrence of atherosclerotic thrombotic events by down-regulating the expression of P2Y12R [ 55 ]. Recently, P2X4R and P2X7R were speculated to be priming molecules in exercise-induced changes in BDNF, and a protective mechanism of exercise is provided in neurogenic diseases (including NPP).…”