Endothelial cell Ass1 inhibits arteriosclerotic calcification in diabetes mellitus

Abstract

Endothelial cell (EC) dysfunction is an important pathological feature of early calcification in diabetic plaques. Argininosuccinic synthase 1 (Ass1) is important in protecting EC activity. Therefore, this study aimed to explore the effect of endothelial Ass1 on calcification in diabetic plaques and its potential regulatory mechanism. In this study, serum Ass1 levels were measured in 84 patients, and the study showed that the serum Ass1 level in patients with diabetes was significantly decreased compared with the non-diabetic group, and the serum Ass1 level in patients with coronary artery calcification was significantly decreased compared with the non-coronary artery calcification group. The ApoE-/- mouse diabetic plaque calcification model and the mouse aortic endothelial cell (MAEC) calcification model were constructed, and the influence of endothelial cell Ass1 on diabetic plaque calcification was further investigated by adeno-associated virus and plasmid intervention. Molecular biology studies have shown that endothelial Ass1 overexpression can reduce plaque calcification and inhibit MAEC osteogenic differentiation in diabetic mice, and Ass1 has protective effects on EC and blood vessels in mice. 4D-label-free proteomic sequencing, bioinformatics analysis, and IP experiments were performed on ApoE-/- mouse aorta after adeno-associated virus intervention. It was found that the differential protein Ptk2b was closely related to vascular calcification (VC) and interacted with the target protein Ass1. The above studies indicate that endothelial Ass1 affects calcification formation in diabetic plaques, and the mechanism may be related to Ptk2b. Ass1 may be a new target for the treatment of diabetic VC.