Protective role of small extracellular vesicles derived from HUVECs treated with AGEs in diabetic vascular calcification

The pathogenesis of vascular calcification in diabetic patients remains elusive. As an effective information transmitter, small extracellular vesicles (sEVs) carry abundant microRNAs (miRNAs) that regulate the physiological and pathological states of recipient cells. In the present study, significant up-regulation of miR-126-5p was observed in sEVs isolated from human umbilical vein endothelial cells (HUVECs) stimulated with advanced glycation end-products (A-EC/sEVs). Intriguingly, these sEVs suppressed the osteogenic differentiation of vascular smooth muscle cells (VSMCs) by targeting BMPR1B, which encodes the receptor for BMP, thereby blocking the smad1/5/9 signalling pathway. In addition, knocking down miR-126-5p in HUVECs significantly diminished the anti-calcification effect of A-EC/sEVs in a mouse model of type 2 diabetes. Overall, miR-126-5p is highly enriched in sEVs derived from AGEs stimulated HUVECs and can target BMPR1B to negatively regulate the trans-differentiation of VSMCs both in vitro and in vivo.

Automated summary

The pathogenesis of vascular calcification in diabetic patients is still not clear. In this study, it was found that small extracellular vesicles (sEVs) secreted by human umbilical vein endothelial cells (HUVECs) stimulated with advanced glycation end-products (AGEs) can target and regulate the calcification-related signaling pathway through miR-126-5p, inhibiting the osteogenic differentiation of vascular smooth muscle cells (VSMCs). Knockdown of miR-126-5p in HUVECs attenuated the anti-calcification effect of sEVs in a mouse model of type 2 diabetes.