Dephosphorylation of circulating human osteopontin correlates with severe valvular calcification in patients with calcific aortic valve disease

Context: Calcific Aortic Valve Disease (CAVD) is an active pathological process leading to biomineralization of the aortic cusps. We characterized circulating and tissue Osteopontin (OPN) as a biomarker for CAVD. Objectives: Here we investigate the post-translational modifications of circulating OPN and correlate the phosphorylation status with the ability to prevent calcification. Methods: Circulating OPN levels were estimated in CAVD patients (n=51) and controls (n=56). In a subgroup of 27 subjects, OPN was purified and the phosphorylation status analyzed. Results: Plasma OPN levels were significantly elevated in CAVD patients as compared to the controls and correlates with the aortic valve calcium score. Our study demonstrates that phospho-threonine levels of OPN purified from controls were higher when compared to CAVD subjects, whereas phospho-serine and phospho-tyrosine levels were comparable between the two groups. Conclusion:The dephosphorylation of circulating OPN correlates with severe valvular calcification in patients with CAVD.