2-Arachidonoylglycerol Attenuates Myocardial Fibrosis in Diabetic Mice Via the TGF-β1/Smad Pathway

Abstract

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.

The mechanisms and therapeutic potential of clopidogrel in mitigating diabetic cardiomyopathy in db/db mice

“…Substantial evidence suggests that inhibiting the TGF-β1/Smad3 pathway can mitigate myocardial fibrosis in diabetic mice. 34 , 35 Consistent with these findings, we found that Clo alleviated cardiac fibrosis in DCM by inhibiting the TGF-β1/Smad3 signaling pathway. Additionally, the ERK, JNK, and p38 signaling pathways were activated in the cardiac tissue of diabetic mice, and Clo treatment suppressed the phosphorylation of ERK and JNK.…”

2-Arachidonoylglycerol in Cardiovascular Disease: Angel or Demon?

“…In this article, the authors found that 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. It indicated that 2-AG is a potential pathway for the treatment of cardiac dysfunction in diabetic mice [1]. Interestingly, in rat isolated hearts subjected to global ischemia/reperfusion, administration of 2-AG before induction of ischemia reduced infarct size.…”

“…Recently, an interesting study entitled "2-Arachidonoylglycerol Attenuates Myocardial Fibrosis in Diabetic Mice Via the TGF-β1/Smad Pathway" was published in Cardiovascular Drugs and Therapy [1]. We congratulate the authors and would like to discuss some points about the role of 2-Arachidonoylglycerol (2-AG) on cardiovascular disease (CVD).…”

Why Multitarget Vasodilatory (Endo)cannabinoids Are Not Effective as Antihypertensive Compounds after Chronic Administration: Comparison of Their Effects on Systemic and Pulmonary Hypertension

“…It should also be kept in mind that the well-known vasodilatory action of eCBs may sometimes be diminished by their vasoconstrictor metabolites, e.g., OEA [58] and AEA, which is even suggested as a PH enhancer (for details, see Section 12) [102]. Similarly, 2-AG can act differently on the vessels (through vasodilation or vasoconstriction) [48,58] and can also have opposite effects on the heart (protective or damaging) [147,148].…”