Identification and Characterization of Calcifying Valve Cells from Human and
Canine Aortic Valves p.254
Emile R. Mohler III, MD, Mohit K. Chawla BS, Alan W. Chang BS, Narendra Vyavahare PhD,
Robert J. Levy MD, Lori Graham BS, Francis H. Gannon MD

Cardiac valve calcification is the predominant pathology in patients needing valve replacement. The purpose of this study was to determine if aortic valve cells calcify spontaneously and, if so, to characterize the nodular complex and response to growth factors. The valvular endothelium was removed from aortic valves and explants cultured in medium. A population of valvular interstitial cells spontaneously formed distinct calcified nodules, containing hydroxyapatite, within two to three weeks in canine and within six weeks with human aortic valves. Cells associated with nodules had osteoblastic-like characteristics and stained positively for extracellular bone matrix proteins. The rate of nodule formation was increased with transforming growth factor beta-1 (+25 nodules), 25-hydroxycholesterol (+9 nodules) and bone morphogenetic protein 2 (+4 nodules) as compared with vehicle control (+3 nodules) over 25 days. In conclusion, we identified a population of valvular interstitial cells with osteoblastic-like characteristics that spontaneously forms calcific nodules in cell culture.