The Effect of Garlic and Voluntary Exercise on Cardiac Angiogenesis in Diabetes: The Role of MiR-126 and MiR-210

Abstract

BackgroundDiabetes mellitus (DM) is one of the major risk factors for cardiovascular disease, leading to endothelial dysfunction and angiogenesis impairment . MiR-126 and miR-210 support angiogenic response in endothelial cells.ObjectiveThe present study sought to explore the effect of garlic and voluntary exercise, alone or together, on miR-126 and miR-210 expressions and cardiac angiogenesis in rats with type 1 diabetes.MethodsMale Wistar rats were divided into five groups (n = 7): Control, Diabetes, Diabetes+Garlic, Diabetes+Exercise, and Diabetes+Garlic+Exercise. Diabetes was induced in the animals by streptozotocin (ip, 50 mg/kg). The rats were then fed raw fresh garlic homogenate (250 mg/kg) or were subjected to voluntary exercise, or to combined garlic and voluntary exercise for 6 weeks. MiR-126 and miR-210 expressions in the myocardium were determined by real time PCR, and the serum lipid profile was measured by enzymatic kits. Angiogenesis was evaluated by immunostaining for PECAM-1/ CD31 in the myocardium.ResultsDiabetes reduced both cardiac miR-126 expression and angiogenesis (p < 0.05). On the other hand, there was a miR-210 expression increase in the myocardium of diabetic animals (p < 0.001). However, those effects reversed either with garlic or voluntary exercise (p < 0.01). Moreover, treating diabetic rats with garlic and voluntary exercise combined had an additional effect on the expressions of miR-126 and miR-210 (p < 0.001). Furthermore, both voluntary exercise and garlic significantly improved serum lipid profiles (p < 0.001).ConclusionThe induction of diabetes decreased angiogenesis in the myocardium, whereas our treatment using long-term voluntary exercise and garlic improved myocardial angiogenesis. These changes were possibly owing to the enhancement of myocardial miR-126 and miR-210 expressions.

The impacts of garlic and voluntary training alone or together on myocardial miR-126 and miR-210 gene expressions and angiogenesis in healthy rats

“…In the current study sample size was defined based on our similar previous investigations. 9 , 17 , 18 …”

“…Dyslipidemia is probably associated with the changes of liver X receptor α expression in some tissues including liver and intestine and also stimulation of NADP which is contributing to eNOS inhibition and impaired angiogenesis. 9 …”

Exercise Mediates Heart Protection via Non-coding RNAs

“…After 8 weeks' voluntary exercise, miR-126, miR-210, Akt, and ERK1/2 in cardiac tissue were upregulated in both the crocin and voluntary exercise groups (Ghorbanzadeh et al, 2017). Another study found that in the diabetic animals there was an decrease of miR-126 and angiogenesis, while the expression level of miR-210 was increased (Naderi et al, 2019). miR-16 decreased, and miR-21 increased after a 5 weeks' high-intensity interval training (HIIT) intervention scenario (Horak et al, 2018).…”

“…MiR-126, known as an endothelial-specific miRNA, targeting sprouty-related protein 1 (SPRED1) and phosphatidyl-inositol 3-kinase regulatory subunit 2 (PIK3R2), activated ERK and Akt, pathways to enhance the role of vascular endothelial growth factor (VEGF) and thus promote the process of angiogenesis (Fernandes et al, 2017). MiR-210, a hypoxia-specific miRNA, may stimulate neovascularization by downregulation of its target gene, ephrin A3, which is an important molecule in VEGF-mediated angiogenesis signaling pathway (Ghorbanzadeh et al, 2017;Naderi et al, 2019). After 8 weeks' voluntary exercise, miR-126, miR-210, Akt, and ERK1/2 in cardiac tissue were upregulated in both the crocin and voluntary exercise groups (Ghorbanzadeh et al, 2017).…”

Dimethylarginine dimethylaminohydrolase-1 contributes to exercise-induced cardiac angiogenesis in mice

“…Inadequate angiogenesis has been viewed as one of the key reasons for the occurrence of these diseases. The cardioprotective effects of regular exercise are an efficient therapeutic strategy to preserve the balance of angiogenesis, including improving cardiac angiogenesis in myocardial infarction (4,5), heart transplantation (6), diabetes (7,8) and aging (9,10). It is well recognized that exercise protects cardiac structure and function via elevating capillary density under pathological conditions (5,11).…”