Why the study?
Diabetic cardiomyopathy causes late cardiac dysfunction with myocardial fibrosis linked to TGF-beta1 up-regulation, and the protective effect of 2-arachidonoylglycerol on diabetic cardiomyopathy required evaluation.
Does 2-Arachidonoylglycerol reduce myocardial fibrosis and improve cardiac function in a diabetic mouse model?
Does 2-Arachidonoylglycerol reduce myocardial fibrosis and improve cardiac function in a diabetic mouse model?
2-Arachidonoylglycerol attenuates myocardial fibrosis and improves cardiac function in diabetic mice by inhibiting the TGF-β1/Smad2/3 pathway.
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May attenuate diabetic cardiomyopathy in models; leaves open clinical translation of 2-AG or TGF-β/Smad targeting.
PURPOSE: Diabetic cardiomyopathy (DM) is the cause of late cardiac dysfunction in diabetic patients. Myocardial fibrosis is the main pathological mechanism, and it is associated with transforming growth factor-β1(TGF-β1) expression up-regulation. 2-Arachidonoylglycerol (2-AG) is an endogenous cannabinoid that can effectively improve myocardial cell energy metabolism and cardiac function. Here, we evaluated the protective effect of 2-AG on diabetic cardiomyopathy. METHODS: Male C57BL/6 mice were injected with 2-AG intraperitoneally for 4 weeks (10 micro g/kg/day) after 12 weeks of diabetic modeling. After 4 weeks, heart function was evaluated by echocardiography. Heart structure was assessed by hematoxylin and eosin staining. Cardiac fibrosis was analyzed using immunohistochemistry, Sirius red stain, and western blot. RESULTS: After modeling in diabetic mice, cardiac ultrasonography showed decreased cardiac function and pathological findings showed myocardial fibrosis. 2-AG could effectively inhibit the up-regulation of TGF-β1 and Smad2/3, reduce myocardial fibrosis, and ultimately improve cardiac function in diabetic mice. CONCLUSION: 2-AG reduces cardiac fibrosis via the TGF-β1/Smad2/3 pathway and is a potential pathway for the treatment of cardiac dysfunction in diabetic mice.
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Chen et al. (2022) studied this question.
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