170 Vasoconstriction Inhibiting Factor: An endogenous inhibitor of vascular calcification as calcimimetic of calcium-sensing receptor

Abstract Background and Aims Patients with chronic kidney disease (CKD), have an increased risk of cardiovascular disease due to the massively accelerated calcification they develop. Vascular calcification is a highly regulated process mediated by different inducers and inhibitors. Recently, the peptide ‘vasoconstriction inhibiting factor’ (VIF) was isolated from bovine adrenal glands and has been described as an inhibitor of the angiotensin II-induced vasoconstriction. Angiotensin II inhibits calcium deposition, but VIF effect on vascular calcification is still unknown. In the present study, VIF has been characterised on vascular calcification assays. Method The effect of VIF was analysed in vitro in human aortic smooth muscle cells (hAoSMC) and ex vivo in rat aortic rings, both cultivated under high phosphate concentrations. VIF was also studied in vivo in rats treated with vitamin D and nicotine (calcification model). Results VIF inhibits calcium deposition in all the models studied. Furthermore, in hAoSMC VIF reduces the production of ROS and the initiation of diverse cascades in the cells, like activation of inflammatory cytokines and MAPK kinases, which in turn trigger the expression of various genes involved in the development of vascular calcification. Furthermore, in presence of VIF the population of apoptotic cells, directly linked to vascular calcification, is decreased. Calcium-sensing receptor (CaSR) has been found as VIF binding partner, pointing to VIF as a new calcimimetic of this receptor, that inhibits vascular calcification by increasing the production of carboxylated Matrix Gla Proteins (cMGP). Conclusion In conclusion, VIF is a new potent endogenous inhibitor of vascular calcification acting as a calcimimetic of CaSR, that leads to an increase cMGP production. This finding represents a basis for a new target for the prevention and therapy of patients with increased vascular calcification and shows an encouraging perspective for the future. Figure: