The association of these biomarkers with CAVD so far has been studied only quantitatively, but the biological activities of these molecules are often controlled by different mechanism(s) like protein-protein interactions and post-translational modifications. Conclusion The dephosphorylation of circulating OPN correlates with severe valvular calcification in patients with CAVD. Introduction Calcific Aortic Valve Disease (CAVD) Emr1 is usually a slow, but progressive, pathological condition of the aortic valve characterized, in its final stage, Canagliflozin by dystrophic calcification of the valve leaflets (Freeman and Otto 2005, Goldbarg et al 2007). It is the most frequent valvular disease, with a prevalence of 3C9%, and the main cause for valve replacement in the adult populace (Bach et al 2007). Despite the high prevalence and mortality associated with aortic valve calcification little is known about its pathological mechanisms. For many decades, the disease has been considered a result of normal aging resulting from prolonged wear and tear of the aortic valve with concomitant passive calcium deposition around the valve leaflets (Cowell et al 2004). However, recent data does not support this simplistic concept. The degeneration of Canagliflozin aortic valve starts with a normal trileaflet aortic valve; initial phases of the disease include moderate thickening of the leaflets (aortic valve sclerosis, AVSc) while more advanced stages are associated with impaired leaflet motion and resistance to forward blood flow (aortic valve stenosis, AVS). The current understanding of the pathophysiological mechanisms underlying CAVD is still not fully elucidated. It has been suggested that mechanical stress, in addition to atherosclerotic risk factors, prospects to valvular endothelial dysfunction/leakage followed by neo-angiogenesis, deposition of lipids and other compounds. This triggers inflammation, thereby activating valvular interstitial cell leading to their osteoblastic transdifferentiation, extracellular matrix remodeling which ultimately prospects to active calcification (Freeman and Otto 2005, Goldbarg et al 2007, OBrien 2006 and Beckmann et al 2010) Clinical examination, echocardiography and cardiac catheterization are the major methods to diagnose CAVD and the treatment of choice for symptomatic AVS is usually aortic valve replacement (AVR) (Cowell et al 2004). Other treatment options, such as percutaneous valve replacement or aortic valvuloplasty, offer some benefits in terms of lower invasiveness and hospitalization time, but are not applicable to all patients (Balmer et al 2004, Perin et al 2009). Canagliflozin Balloon aortic valvuloplasty is usually a well-established and well-studied process with nontrivial complication rates, very high rates of recurrent stenosis and moderately high rates of aortic insufficiency (Balmer et al. 2004, Wang et al 1997). Recently completed PARTNER trial on percutaneous aortic valve implantation in inoperable patients with severe aortic stenosis shows significantly reduced death rates in patients and significant improvements in health-related quality of life that were managed for at least 1 year (Leon et al 2010, Reynolds et al 2011). However long term performance of these prostheses remains unknown at the present time. Mineralization of bioprostheses is also a major contributor to failure (Siddiqui, Abraham and Butany 2009). The mechanisms involved in dystrophic calcification of these valves are believed to resemble closely the bio-mineralization process in native aortic valves (Freeman and Otto 2005, Speer and Giachelli 2004). Notably, surgical valve replacement in any of its forms leaves the underlying mechanism that caused the original valvular degeneration, untreated. Acceleration of valve failure of either native or bioprosthetic valves is usually attributed to active calcium deposition and degeneration of the leaflets. The calcification of aortic bio-prostheses suggests that circulating molecules implicated in the regulation of bio-mineralization must be involved in the calcification process. Osteopontin (OPN) is a multifunctional glycol-phospho-protein that plays an important role in bone remodeling via differentiation and stimulation of osteoclasts. Besides its function in bone tissue, OPN Canagliflozin is also implicated in a variety of acute, as well as, chronic inflammatory processes, including wound healing, fibrosis and atherosclerosis (Cho et al 2009). Furthermore, OPN is involved in the biomineralization of dystrophic and ectopic sites, including the aortic valve.