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

Autor: Jae-Joon Jung, Azmi A. Ahmad, Saranya Rajendran, Linyan Wei, Jiasheng Zhang, Jakub Toczek, Lei Nie, Gunjan Kukreja, Mani Salarian, Kiran Gona, Mean Ghim, Raja Chakraborty, Kathleen A. Martin, George Tellides, Donald Heistad, Mehran M. Sadeghi
Rok vydání: 2022
Předmět:
Zdroj: JACC: Basic to Translational Science. 7:333-345
ISSN: 2452-302X
DOI: 10.1016/j.jacbts.2021.12.006
Popis: 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.
Databáze: OpenAIRE