Autophagy reduces aortic calcification in diabetic mice by reducing matrix vesicle body-mediated IL-1 release

Vascular calcification (VC) is a common pathological process of cardiovascular disease that occurs in patients with type 2 diabetes mellitus (T2DM). However, the molecular basis of VC progression remains unknown. A GEO dataset (GSE146638) was analyzed to show that microbodies and IL-1 beta may play important roles in the path-ophysiology of VC. The release of matrix vesicle bodies (MVBs) and IL-1 beta and the colocalization of IL-1 beta with MVBs or autophagosomes were studied by immunofluorescence in an in vivo diabetes mouse model with aortic calcification and an in vitro high glucose cell calcification model. MVB numbers, IL-1 beta levels and autophagy were increased in calcified mouse aortas and calcified vascular smooth muscle cells (VSMCs). IL-1 beta colocalized with MVBs and autophagosomes. The MVBs from calcified VSMCs induced the calcification of normal recipient VSMCs, and this effect was alleviated by silencing IL-1 beta. The autophagy inducer rapamycin reduced IL-1 beta expression and calcification in VSMCs, while these processes were induced by the autophagy inhibitor chloro-quine. In conclusion, our results suggested that MVBs could carry IL-1 beta out of cells and induce VC in normal VSMCs, and these processes could be counteracted by autophagy. These results suggested that MVB-mediated IL-1 beta release may be an effective target for treating vascular calcification.