Journal article
Differential BMP Signaling Mediates the Interplay Between Genetics and Leaflet Numbers in Aortic Valve Calcification
JACC. Basic to translational science, Vol.7(4), pp.333-345
04/2022
DOI: 10.1016/j.jacbts.2021.12.006
PMCID: PMC9079798
PMID: 35540096
Abstract
[Display omitted]
•The neuropilin-like protein, DCBLD2, is down-regulated in aortic valves of patients undergoing valve replacement for aortic stenosis.•About 50% of DCBLD2-deficient mice develop bicuspid aortic valve. These animals have a high prevalence of calcific aortic valve disease with typical features of human disease, including aortic stenosis.•DCBLD2 down-regulation up-regulates bone morphogenic protein 2, a key mediator of calcification. Despite a similar level of bone morphogenic protein 2 between bicuspid and tricuspid aortic valves, downstream signaling and expression of the calcification marker, osteocalcin are more pronounced in bicuspid aortic valves.•Introducing a clinically relevant model of calcific aortic valve disease, these findings may explain how a combination of genetic background and bicuspid aortic valve promotes aortic valve calcification and stenosis.
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.
Details
- Title: Subtitle
- Differential BMP Signaling Mediates the Interplay Between Genetics and Leaflet Numbers in Aortic Valve Calcification
- Creators
- Jae-Joon Jung - Yale UniversityAzmi A. Ahmad - Yale UniversitySaranya Rajendran - Yale UniversityLinyan Wei - Yale UniversityJiasheng Zhang - Yale UniversityJakub Toczek - Yale UniversityLei Nie - Yale UniversityGunjan Kukreja - Yale UniversityMani Salarian - Yale UniversityKiran Gona - Yale UniversityMean Ghim - Yale UniversityRaja Chakraborty - Yale UniversityKathleen A. Martin - Yale UniversityGeorge Tellides - Yale UniversityDonald Heistad - University of IowaMehran M. Sadeghi - Yale University
- Resource Type
- Journal article
- Publication Details
- JACC. Basic to translational science, Vol.7(4), pp.333-345
- DOI
- 10.1016/j.jacbts.2021.12.006
- PMID
- 35540096
- PMCID
- PMC9079798
- NLM abbreviation
- JACC Basic Transl Sci
- ISSN
- 2452-302X
- eISSN
- 2452-302X
- Publisher
- Elsevier Inc
- Language
- English
- Date published
- 04/2022
- Academic Unit
- Cardiovascular Medicine; Neuroscience and Pharmacology; Internal Medicine
- Record Identifier
- 9984303857102771
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