RESUMO
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-1ß may play important roles in the pathophysiology of VC. The release of matrix vesicle bodies (MVBs) and IL-1ß and the colocalization of IL-1ß 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-1ß levels and autophagy were increased in calcified mouse aortas and calcified vascular smooth muscle cells (VSMCs). IL-1ß 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-1ß. The autophagy inducer rapamycin reduced IL-1ß expression and calcification in VSMCs, while these processes were induced by the autophagy inhibitor chloroquine. In conclusion, our results suggested that MVBs could carry IL-1ß out of cells and induce VC in normal VSMCs, and these processes could be counteracted by autophagy. These results suggested that MVB-mediated IL-1ß release may be an effective target for treating vascular calcification.
