Key result
Inhibition of miR-21 alleviated cardiac perivascular fibrosis and improved cardiac function in diabetic cardiomyopathy by suppressing EndMT via the NF-κB/miR-21/SMAD7 pathway.
Why the study?
To explore the molecular mechanism of miR-21 regulating endothelial-mesenchymal transition and cardiac perivascular fibrosis in diabetic cardiomyopathy.
Does inhibition of miR-21 alleviate cardiac perivascular fibrosis and EndMT in T1DM models?
Does inhibition of miR-21 alleviate cardiac perivascular fibrosis and EndMT in T1DM models?
Inhibition of miR-21 alleviates cardiac perivascular fibrosis in diabetic cardiomyopathy by suppressing EndMT via the NF-κB/miR-21/SMAD7 pathway, presenting a potential therapeutic target.
miR-21 inhibition shows promise in T1DM animal models; leaves open clinical translation pending human trials.
In type 1 and type 2 diabetes mellitus, increased cardiac fibrosis, stiffness and associated diastolic dysfunction may be the earliest pathological phenomena in diabetic cardiomyopathy. Endothelial-mesenchymal transition (EndMT) in endothelia cells (ECs) is a critical cellular phenomenon that increases cardiac fibroblasts (CFs) and cardiac fibrosis in diabetic hearts. The purpose of this paper is to explore the molecular mechanism of miR-21 regulating EndMT and cardiac perivascular fibrosis in diabetic cardiomyopathy. In vivo, hyperglycaemia up-regulated the mRNA level of miR-21, aggravated cardiac dysfunction and collagen deposition. The condition was recovered by inhibition of miR-21 following with improving cardiac function and decreasing collagen deposition. miR-21 inhibition decreased cardiac perivascular fibrosis by suppressing EndMT and up-regulating SMAD7 whereas activating p-SMAD2 and p-SMAD3. In vitro, high glucose (HG) up-regulated miR-21 and induced EndMT in ECs, which was decreased by inhibition of miR-21. A highly conserved binding site of NF-κB located in miR-21 5'-UTR was identified. In ECs, SMAD7 is directly regulated by miR-21. In conclusion, the pathway of NF-κB/miR-21/SMAD7 regulated the process of EndMT in T1DM, in diabetic cardiomyopathy, which may be regarded as a potential clinical therapeutic target for cardiac perivascular fibrosis.
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Yao et al. (2019) studied Type 1 Diabetes Mellitus and Diabetic Cardiomyopathy. Inhibition of miR-21 was evaluated on Cardiac perivascular fibrosis and EndMT. Inhibition of miR-21 alleviated cardiac perivascular fibrosis and improved cardiac function in diabetic cardiomyopathy by suppressing EndMT via the NF-κB/miR-21/SMAD7 pathway.
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