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

ABSTRACT: 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.

SUBMITTER: Jung JJ 

PROVIDER: S-EPMC9079798 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature

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

Jung Jae-Joon JJ   Ahmad Azmi A AA   Rajendran Saranya S   Wei Linyan L   Zhang Jiasheng J   Toczek Jakub J   Nie Lei L   Kukreja Gunjan G   Salarian Mani M   Gona Kiran K   Ghim Mean M   Chakraborty Raja R   Martin Kathleen A KA   Tellides George G   Heistad Donald D   Sadeghi Mehran M MM  

JACC. Basic to translational science 20220323 4

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  ...[more]

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