Résumé
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 the effect of the VIF peptide on vascular calcification is still unknown. In the present study, we have characterised VIF on vascular calcification assays.
Method
The effect of the VIF peptide was analysed in vitro in human aortic smooth muscle cells (hAoSMC) and ex vivo in rat aortic rings, both cultivated under high phosphate concentrations to induce calcification. VIF was also studied in vivo in rats treated with vitamin D and nicotine (as a calcification model).
Results
VIF peptide inhibits calcium deposition in all the models studied. Furthermore, in hAoSMC the VIF peptide 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 the VIF peptide the population of apoptotic cells, directly linked to vascular calcification, is decreased. Calcium-sensing receptor (CaSR) has been found as binding partner of the VIF peptide, pointing to VIF as a new calcimimetic of this receptor, that inhibits vascular calcification by increasing the production of carboxylated Matrix Gla Proteins (cMGP). Moreover, CKD patients show a negative correlation between their degree of calcification in the aorta and the concentration the VIF peptide in plasma.
Conclusion
In conclusion, the VIF peptide is a new calcimimetic of CaSR that acts as a potent endogenous inhibitor of vascular calcification by increasing 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 1: