ABC | Volume 112, Nº2, February 2019

Original Article The Effect of Garlic and Voluntary Exercise on Cardiac Angiogenesis in Diabetes: The Role of MiR-126 and MiR-210 Roya Naderi, 1,2 Gisou Mohaddes, 3 Mustafa Mohammadi, 4 Alireza Alihemmati, 5 Amirmahdi Khamaneh, 6 Rafighe Ghyasi, 4 Rana Ghaznavi 7 Nephrology and Kidney Transplant Research Center - Urmia University of Medical Sciences, 1 Urmia - Iran Department of Physiology, faculty of Medicine - Urmia University of Medical Sciences, 2 Urmia - Iran Neuroscience Research Centre of Tabriz University of Medical Sciences, 3 Tabriz - Iran Drug Applied Research Center of Tabriz University of Medical Sciences, 4 Tabriz - Iran Department of Histology and Embryology, Faculty of Medicine, Tabriz University of Medical Sciences, 5 Tabriz - Iran School of advanced medical sciences - Tabriz University of Medical Sciences, 6 Tabriz - Iran Sports medicine research center, Neuroscience institute - Tehran University of Medical Sciences, 7 Tehran - Iran Correspondência: Mustafa Mohammadi • Drug Applied Research Center of Tabriz University of Medical Sciences, Tabriz -Iran E-mail: m.mohammadin@yahoo.com Manuscript received February 05, 2018, revised manuscript August 02, 2018, accepted August 02, 2018 DOI: 10.5935/abc.20190002 Abstract Background: Diabetes 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. Objective: The 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. Methods: Male 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. Results: Diabetes 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). Conclusion: The 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. (Arq Bras Cardiol. 2019; 112(2):154-162) Keywords: Rats; Garlic; Allium Sativum; Exercise; Diabetes Mellitus; microRNAs ; Angiogenesis Inducing Agents; Neovascularization; Physologic. Introduction Diabetes mellitus (DM) is one of the major risk factors for cardiovascular disease, leading to endothelial dysfunction and angiogenesis impairment. 1 The current trend on research and health care focuses on providing effective therapy with few side effects and low toxicity that can be regularly used to control diabetes complications. 2 Exercise is a powerful therapeutic strategy to improve overall cardiovascular health. 3 However, exhaustive exercise may be problematic as it can cause the production of reactive oxygen species (ROS). 4 Therefore, voluntary exercise, in which the animal has free access to a running wheel, may be a model with more positive effects. 5 There is evidence that aerobic training can promote cardiac angiogenesis, 6,7 in which the vascular endothelial growth factor (VEGF) has a critical role. 5 However, the underlying mechanisms of exercise have yet to be fully elucidated. One of the most traditional plants in herbal medicine is Allium sativum L , which has been reported to have beneficial health effects. It is used as a therapeutic agent in various disorders such as cancer, cardiovascular disease, and diabetes through different mechanisms, including inhibition or stimulation of angiogenesis. 2,8,9 Considering the effects of garlic in protecting against cardiovascular disease, as well as its effects on angiogenesis in different tissues, it is interesting to examine the effects of garlic on both myocardial angiogenesis and its related mechanisms. 154