 |
Journal articles
Reduced aggrecan expression affects cardiac outflow tract development in zebrafish and is associated with bicuspid aortic valve disease in humans
Abstract : Available online xxxx Hemodynamic forces have been known for a long time to regulate cardiogenic processes such as cardiac valve development. During embryonic development in vertebrates, the outflow tract (OFT) adjacent to the ventricle comes under increasing hemodynamic load as cardiogenesis proceeds. Consequently, extracellular matrix components are produced in this region as the cardiac cushions form which will eventually give rise to the aortic valves. The proteoglycan AGGRECAN is a key component of the aortic valves and is frequently found to be deregulated in a variety of aortic valve diseases. Here we demonstrate that aggrecan expression in the OFT of developing zebrafish embryos is hemodynamically dependent, a process presumably mediated by mechanosensitive channels. Furthermore, knockdown or knockout of aggrecan leads to failure of the OFT to develop resulting in ste-nosis. Based on these findings we analysed the expression of AGGRECAN in human bicuspid aortic valves (BAV). We found that in type 0 BAV there was a significant reduction in the expression of AGGRECAN. Our data indicate that aggrecan is required for OFT development and when its expression is reduced this is associated with BAV in humans.
Cited literature [16 references]
https://www.hal.inserm.fr/inserm-01617193
Contributor : Adèle Faucherre <>
Submitted on : Thursday, March 29, 2018 - 10:04:07 AM
Last modification on : Friday, November 6, 2020 - 3:11:16 AM
Long-term archiving on: : Thursday, September 13, 2018 - 12:07:25 PM
Contributor : Adèle Faucherre <>
Submitted on : Thursday, March 29, 2018 - 10:04:07 AM
Last modification on : Friday, November 6, 2020 - 3:11:16 AM
Long-term archiving on: : Thursday, September 13, 2018 - 12:07:25 PM
File
RambeaudIntJCardiol2017.pdf
Files produced by the author(s)