Vascular calcification is strongly associated with increased cardiovascular mortality and morbidity. C1q/TNF-related protein-13 (CTRP13) is a secreted adipokine that plays important roles in the cardiovascular system. However, the functional role of CTRP13 in the development of vascular calcification has yet to be explored. In this study, we collected blood samples from patients with chronic renal failure (CRF) and from rats with adenine-induced CRF. We found that the serum CTRP13 levels were decreased in patients and rats with CRF and were negatively associated with calcium deposition in the abdominal aorta. Compared to those of the controls, ectopic CTRP13 treatment significantly attenuated the calcium accumulation and alkaline phosphatase activity in the abdominal aorta of CRF rats, and β-glycerophosphate induced the formation of arterial rings and of vascular smooth muscle cells (VSMCs) and decreased the number of VSMCs that transitioned from a contractile to an osteogenic phenotype. The overexpression of Runx2 blocked CTRP13-reduced VSMC calcification. Mechanistically, CTRP13 repressed the phosphorylation of tristetraprolin (TTP), thereby activating TTP and increasing the TTP binding to the 3'untranslated region of the Runx2 mRNA, accelerating the Runx2 mRNA destabilization and degradation. In summary, these findings reveal that CTRP13 regulation is a novel method for the prevention of vascular calcification, representing a novel mechanism of the regulation of Runx2 expression in VSMCs.-Li, Y., Wang, W., Chao, Y., Zhang, F., Wang, C. CTRP13 attenuates vascular calcification by regulating Runx2.
Keywords: chronic renal failure; mRNA decay; phenotypic switch; vascular smooth muscle cells.