Calcific aortic valve disease (CAVD) is a significant cause of morbidity and mortality, which affects ≈1% of the US population and is characterized by calcific nodule formation and stenosis of the valve. Klotho-deficient mice were used to study the molecular mechanisms of CAVD as they develop robust aortic valve (AoV) calcification. Through microarray analysis of AoV tissues from klotho-deficient and wild-type mice, increased expression of the gene encoding cyclooxygenase 2 (COX2; Ptgs2) was found. COX2 activity contributes to bone differentiation and homeostasis, thus the contribution of COX2 activity to AoV calcification was assessed.