Molecular Mechanisms of Aortic Valve Calcification

Calcific aortic stenosis is the most frequent heart valve disease and the main cause of valve replacement in patients over the age of 60. Despite the high prevalence and mortality associated with aortic valve calcification and aortic stenosis, little is known about its pathogenetic mechanisms. Osteopontin, a multifunctional protein implicated in the regulation of physiological calcification and biomineralization, has generated significant interest for its potential role in the pathogenesis of calcific valvular disease. Surprisingly, although osteopontin inhibits calcification, elevated levels of osteopontin are present in the heart valves of patients with calcified valvular disease. Recent studies by us and other groups have shown a correlation between increased plasma osteopontin levels and valvular calcification. However, all studies have been limited to the quantitative assessment of osteopontin. Our present work focuses on qualitative changes in the osteopontin molecule that can alter its biological function. The ultimate goal of our work is to develop predictors for the degree and progression of aortic stenosis, and to identify potential therapeutic targets for this prevalent and significant disease.

Our Research Faculty

Leora Balsam, MD
Assistant Professor of Cardiothoracic Surgery

Paolo Mignatti, PhD
Associate Professor of Cardiothoracic Surgery and Cell Biology

Giuseppe Pintucci, PhD
Assistant Professor of Cardiothoracic Surgery