Differential BMP Signaling Mediates the Interplay Between Genetics and Leaflet Numbers in Aortic Valve Calcification.

Expression of a neuropilin-like protein, DCBLD2, is reduced in human calcific aortic valve disease (CAVD). DCBLD2-deficient mice develop bicuspid aortic valve (BAV) and CAVD, which is more severe in BAV mice compared with tricuspid littermates. In vivo and in vitro studies link this observation to up-regulated bone morphogenic protein (BMP)2 expression in the presence of DCBLD2 down-regulation, and enhanced BMP2 signaling in BAV, indicating that a combination of genetics and BAV promotes aortic valve calcification and stenosis. This pathway may be a therapeutic target to prevent CAVD progression in BAV.
Competing Interests: This work was supported by grants from the National Institutes of Health (NIH) grants R01AG065917 and R01HL138567. and Department of Veterans Affairs grant I0-BX004038. Dr Salarian was supported by National Institutes of Health training grant 5T32HL007950. The resources of the Yale Translational Research Imaging Center, funded in part by National Institutes of Health grant 1S10RR018039, were used for this study. The authors have reported that they have no relationships relevant to the contents of this paper to disclose.