A novel protective role of lipoxin in inhibiting diabetic vascular calcification via YAP signalling: Health prevention and regulation

Abstract

Vascular calcification is highly prevalent in diabetes patients, with detrimental consequences and no effective prevention and treatment strategies are currently available. Though the protective effect of lipoxin (LX) against vascular diseases has been demonstrated, its effect on diabetic vascular calcification remains unknown. AGEs dose-dependently induced calcification and the expression of osteogenesis-related markers, coupled with the activation of yes-associated protein (YAP). Mechanistically, YAP activation enhanced the AGE-induced osteogenic phenotype and calcification, but inhibition of YAP signalling alleviated this response. Further, an in vivo diabetic mouse model was established using a combination of a high-fat diet and multiple formulations of low-dose streptozotocin. Consistent with the in vitro results, diabetes promoted YAP expression and its subcellular localization in the nucleus in the arterial tunica media. The results demonstrate that LX attenuates the trans-differentiation and calcification of VSMCs in diabetes mellitus via YAP signalling, suggesting LX to be a potent therapeutic for preventing diabetic vascular calcification.

Keywords: Advanced glycation end products; Lipoxin; Vascular calcification; Vascular smooth muscle cells; Yes-associated protein.