Bone morphogenetic protein-2 may represent the molecular link between oxidative stress and vascular stiffness in chronic kidney disease.
Oxidative stress and vascular calcifications are emergent risk factors for the accelerated atherosclerosis process featuring chronic kidney disease (CKD). Vascular calcification is an active process similar to bone modelling, where BMP-2 may play a pathogenic role. Aim of our study was to investigate the link between oxidative stress, BMP-2 protein expression and vascular disease in CKD. We enrolled 85 CKD patients (K-DOQI stage II or higher) and 41 healthy individuals. 8-Oxo-7,8-dihydro-2'-deoxyguanosine (8-OHdG) was used as a marker of oxidative stress. Brachial-ankle pulse wave velocity (baPWV) was used as a measure of arterial stiffness. BMP-2 serum levels were significantly higher in CKD patients than in controls (p<0.0001). Serum 8-OHdG levels were significantly higher in CKD patients compared to controls (p<0.05). BMP-2 serum levels were inversely associated with eGFR (r=-0.3; p=0.01) and directly correlated with 8-OHdG serum concentrations (r=-0.3; p=0.03). Arterial stiffness was inversely correlated with eGFR (r=-0.4; p=0.001) and directly correlated with BMP-2 (r=0.3; p=0.03), 8-OHdG (r=0.4, p=0.02) and phosphorus serum levels (r=0.3; p=0.007). In a multiple regression model, phosphorus and BMP-2 were independently correlated with baPWV. In vitro exposure to H(2)O(2) induced a time and dose-dependent increase in BMP-2 expression in an immortalized endothelial cell line. Moreover, H(2)O(2) pre-incubation of cultured vascular smooth muscle cell enhanced the BMP-2-induced up-regulation of ALPL, an osteoblastic phenotype marker. Our data suggest that in CKD BMP-2 may represent the molecular link between oxidative stress and arterial stiffness due to vascular calcification.
Dalfino
G
G
Renal, Transplantation and Dialysis Unit, Department of Emergency and Organ Transplantation, University of Bari, Piazza Giulio Cesare 11, 70124 Bari, Italy.
Simone
S
S
Porreca
S
S
Cosola
C
C
Balestra
C
C
Manno
C
C
Schena
F P
FP
Grandaliano
G
G
Pertosa
G
G
D000328:Adult; D000368:Aged; D055396:Bone Morphogenetic Protein 2 / Q000378:metabolism*; D002318:Cardiovascular Diseases / Q000097:blood; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D007676:Kidney Failure, Chronic / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D032389:Myocytes, Smooth Muscle / Q000166:cytology; D010006:Osteoblasts / Q000378:metabolism; D018384:Oxidative Stress; D010758:Phosphorus / Q000097:blood; D015854:Up-Regulation
D055396:Bone Morphogenetic Protein 2; D010758:Phosphorus