AUTHORS
Jiayu Zhong, MingHao Yuan, Shuo Hu, En Zhou
ABSTRACT
Diabetes is a prevalent metabolic condition that is closely linked to aging, and its biggest associated risk is vascular related complications. The calcification and aging of blood vessels in diabetes play a significant role in the development of diabetic vascular complications. Growing evidence links exosomal microRNA to the process of diabetic vascular complications. The present study aims to explore the expression, regulatory mechanisms and functions of exosomal miR-6499-3p in the process of diabetic vascular complications. VSMCs could take up exosomes isolated from HUVEC(ECs-exosome) treated with high glucose(HG). These exosomes induced the calcification and senescence of VSMCs through a paracrine mechanism. We then found that HG elevated the expression level of miR-6499-3p both in HUVECs and ECs-exosome. Calcification and senescence of VSMCs can be promoted by ECs-exosomes following overexpression of miR-6499-3p. Furthermore, we demonstrated that the effects of exosomes on the calcification and senescence of VSMCs is mediated by Sclerosin-containing domain SOSTDC1, the potential target of the miR-6499-3p. Our data has shown that a specific role of exosomes from HG-treated HUVEC in regulating the calcification and senescence of VSMCs in a paracrine manner through the miR-6499-3p/SOSTDC1 pathway. Modulation of exosomal miR-6499-3p may provide a novel perspective on the treatment of diabetic vascular complications.