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Correlation Between Osteopontin Levels And Aortic Valve Calcification: Potential Insights Into The Pathogenesis Of Valve Aortic Calcification
P. Yu, A. Skolnick, G. Ferrari, K. Heretis, P. Mignatti, G. Pintucci, B. Rosenzweig, J. Diaz-Cartelle, I. Kronzon, G. Perk, H. I. Pass, A. Galloway, E. A. Grossi, J. Grau. New York University School of Medicine, New York, NY,
BACKGROUND: The inflammatory process of aortic stenosis (AS) results in the differentiation of myofibroblasts, native to aortic valve leaflets, into osteoblasts. Osteopontin (OPN), a proinflammatory glycoprotein, both stimulates differentiation of myofibroblasts and regulates the deposition of calcium by osteoblasts. OPN is elevated in patients with such conditions as endstage renal disease, ectopic calcification, and autoimmune disease. We hypothesized that elevated OPN levels may be associated with the presence of aortic valve calcification (AVC).
METHODS: Venous blood from volunteers over 65 years of age undergoing outpatient echocardiography and from patients scheduled for aortic valve surgery for AS were collected after obtaining informed consent. Plasma OPN levels were measured by Enzyme-Linked Immuno Sorbent Assay (ELISA). The presence of any AS was defined as aortic valve area <2.0cm2. AVC was assessed using a validated echocardiographic grading system (1=none, 2=mild, 3=moderate, 4=severe). Data is presented as mean± standard deviation; comparisons were performed using non-paired t-tests.
RESULTS: AS was present in 24 patients (mean age 78yrs) and was not present in 7 patients (mean age 72yrs; p=NS). AVC was 3.5±0.58 in AS patients and 1.3±0.49 in patients without AS (p<0.001). Patients with no or mild AVC had lower OPN levels as compared to patients with moderate or severe AVC (406.1±165.8ng/mL vs 629.5+227.5ng/mL, p<0.02). Similarly, patients with AS had significantly higher OPN levels as compared to patients without AS (649.0±221.5ng/mL vs 379.7±159.8ng/mL, p<0.01, Graph 1).
CONCLUSION: Elevated levels of plasma OPN are associated with the presence of AVC and AS. These findings suggest that OPN may play a functional role in the pathogenesis of calcific AS.
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