BMP Signaling is Required for Aortic Valve Calcification

Objective Calcific Aortic Valve Disease (CAVD) is the most prevalent type of heart valve disease, affecting ~2% of the US population. CAVD is characterized by the presence of calcific nodules resulting in aortic valve (AoV) stenosis; however, the underlying mechanisms driving disease remain unknown. Studies of human diseased AoV provide initial evidence that BMP signaling, essential for normal bone formation, is activated during CAVD. Mice deficient in Klotho, an FGF23 transmembrane co-receptor, exhibit premature aging and develop AoV calcific nodules as occurs in human CAVD. The role of BMP signaling in the development of CAVD was examined in porcine aortic valve interstitial cells (VICs) and Klotho−/− mice.