The role of osteoprotegerin, rank-ligand, matrix-gla protein and C-type natriuretic peptide on the carotid atherosclerosis in normal and diabetic subjects

Abstract: Vascular calcification, a degenerative process considered in the past to be a passive procedure, has now been suggested as being related to the ossification process. Several factors known to be involved in the process of bone formation have been identified also on arterial walls. Among these the osteoprogeterin OPG/RANKL/RANK axis and the vitamin K dependentmatrix GLA protein (MGP) have been reported to play an important role in the atherosclerotic process. Finally, C-type natriuretic peptide (CNP) plays a central role in the control of vasculature tone and in several clinical conditions characterized by endothelial dysfunction. This study aimed to investigate the relationships between OPG, RANKL, MGPand NT-pro CNP serum levels and carotid atherosclerosis. We studied 273 subjects, 178 normals and 95 with type 2 diabetes (DM2), (mean age: 56.6± 7.5 yrs). In all subjects we measured OPG, RANKL, MGP and NT proCNP serum levels by ELISA methods. Bone Mineral Density (BMD) at lumbar spine (BMD-LS) and at femur (neck: BMD-FN; total:BMD-FT)were alsomeasured.Anultrasound examination of carotid vesselswas performedto assess intima-media-thickness (IMT), presence of plaque and the degree of calcification. In both normals and DM2 patients the presence of osteoporosis (T-Score<−2.5) was significantly associated to amore severe carotid atherosclerosis, but the relationship between BMD and carotid atherosclerosis resulted lower in DM2 than in normal subjects. MGP resulted significantly lower in DM2 patients than in normal subjects (7.39±2.2 nmol/l vs 12.9±6.4 nmol/l; p<0.01). In both normal subjects and DM2 patientsMGPwas inversely associated with carotid stenosis (r=−0.15; p<0.05andr=−0.17; p<0.05).Asignificant correlation betweenMGP and IMTwas found only in DM2 patients (r=−0.17; p<0.05). OPG resulted higher in DM2 patients than in normal subjects. NT-proCNP was lower in DM2 patients than in normals (p<0.05); moreover NT-proCNP was inversely associatedwith carotid stenosis in DM2 patients (p<0.05) but not in normal subjects. In conclusion, our findings seem to demonstrate that OPG, MGP and NT-proCNP play an important role in the carotid atherosclerotic process, so confirming the presence of links between mineral metabolism and cardiovascular diseases.