差异性骨形态发生蛋白信号传导介导主动脉瓣钙化中基因与瓣叶数量之间的相互作用。
Differential BMP Signaling Mediates the Interplay Between Genetics and Leaflet Numbers in Aortic Valve Calcification.
作者信息
Jung Jae-Joon, Ahmad Azmi A, Rajendran Saranya, Wei Linyan, Zhang Jiasheng, Toczek Jakub, Nie Lei, Kukreja Gunjan, Salarian Mani, Gona Kiran, Ghim Mean, Chakraborty Raja, Martin Kathleen A, Tellides George, Heistad Donald, Sadeghi Mehran M
机构信息
Section of Cardiovascular Medicine and Cardiovascular Research Center, Yale University School of Medicine, New Haven, Connecticut, USA.
VA Connecticut Healthcare System, West Haven, Connecticut, USA.
出版信息
JACC Basic Transl Sci. 2022 Mar 23;7(4):333-345. doi: 10.1016/j.jacbts.2021.12.006. eCollection 2022 Apr.
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.
一种类神经纤毛蛋白DCBLD2在人类钙化性主动脉瓣疾病（CAVD）中表达降低。DCBLD2基因缺陷的小鼠会出现二叶式主动脉瓣（BAV）和CAVD，与同窝出生的三叶式主动脉瓣小鼠相比，BAV小鼠的病情更严重。体内和体外研究表明，这一现象与DCBLD2表达下调时骨形态发生蛋白（BMP）2表达上调以及BAV中BMP2信号增强有关，这表明遗传学因素与BAV共同作用会促进主动脉瓣钙化和狭窄。该通路可能是预防BAV中CAVD进展的治疗靶点。
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