Collagen fiber regulation in human pediatric aortic valve development and disease
Abstract Congenital aortic valve stenosis (CAVS) affects up to 10% of the world population without medical therapies to treat the disease. New molecular targets are continually being sought that can halt CAVS progression. Collagen deregulation is a hallmark of CAVS yet remains mostly undefined. Here...
Guardado en:
Autores principales: | , , , , , , , , , , , |
---|---|
Formato: | article |
Lenguaje: | EN |
Publicado: |
Nature Portfolio
2021
|
Materias: | |
Acceso en línea: | https://doaj.org/article/f870ac3e8279454988ad55f7c7a0b959 |
Etiquetas: |
Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
|
id |
oai:doaj.org-article:f870ac3e8279454988ad55f7c7a0b959 |
---|---|
record_format |
dspace |
spelling |
oai:doaj.org-article:f870ac3e8279454988ad55f7c7a0b9592021-12-02T14:29:15ZCollagen fiber regulation in human pediatric aortic valve development and disease10.1038/s41598-021-89164-w2045-2322https://doaj.org/article/f870ac3e8279454988ad55f7c7a0b9592021-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-89164-whttps://doaj.org/toc/2045-2322Abstract Congenital aortic valve stenosis (CAVS) affects up to 10% of the world population without medical therapies to treat the disease. New molecular targets are continually being sought that can halt CAVS progression. Collagen deregulation is a hallmark of CAVS yet remains mostly undefined. Here, histological studies were paired with high resolution accurate mass (HRAM) collagen-targeting proteomics to investigate collagen fiber production with collagen regulation associated with human AV development and pediatric end-stage CAVS (pCAVS). Histological studies identified collagen fiber realignment and unique regions of high-density collagen in pCAVS. Proteomic analysis reported specific collagen peptides are modified by hydroxylated prolines (HYP), a post-translational modification critical to stabilizing the collagen triple helix. Quantitative data analysis reported significant regulation of collagen HYP sites across patient categories. Non-collagen type ECM proteins identified (26 of the 44 total proteins) have direct interactions in collagen synthesis, regulation, or modification. Network analysis identified BAMBI (BMP and Activin Membrane Bound Inhibitor) as a potential upstream regulator of the collagen interactome. This is the first study to detail the collagen types and HYP modifications associated with human AV development and pCAVS. We anticipate that this study will inform new therapeutic avenues that inhibit valvular degradation in pCAVS and engineered options for valve replacement.Cassandra L. CliftYan Ru SuDavid BichellHeather C. Jensen SmithJennifer R. BethardKim Norris-CanedaSusana Comte-WaltersLauren E. BallM. A. HollingsworthAnand S. MehtaRichard R. DrakePeggi M. AngelNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-17 (2021) |
institution |
DOAJ |
collection |
DOAJ |
language |
EN |
topic |
Medicine R Science Q |
spellingShingle |
Medicine R Science Q Cassandra L. Clift Yan Ru Su David Bichell Heather C. Jensen Smith Jennifer R. Bethard Kim Norris-Caneda Susana Comte-Walters Lauren E. Ball M. A. Hollingsworth Anand S. Mehta Richard R. Drake Peggi M. Angel Collagen fiber regulation in human pediatric aortic valve development and disease |
description |
Abstract Congenital aortic valve stenosis (CAVS) affects up to 10% of the world population without medical therapies to treat the disease. New molecular targets are continually being sought that can halt CAVS progression. Collagen deregulation is a hallmark of CAVS yet remains mostly undefined. Here, histological studies were paired with high resolution accurate mass (HRAM) collagen-targeting proteomics to investigate collagen fiber production with collagen regulation associated with human AV development and pediatric end-stage CAVS (pCAVS). Histological studies identified collagen fiber realignment and unique regions of high-density collagen in pCAVS. Proteomic analysis reported specific collagen peptides are modified by hydroxylated prolines (HYP), a post-translational modification critical to stabilizing the collagen triple helix. Quantitative data analysis reported significant regulation of collagen HYP sites across patient categories. Non-collagen type ECM proteins identified (26 of the 44 total proteins) have direct interactions in collagen synthesis, regulation, or modification. Network analysis identified BAMBI (BMP and Activin Membrane Bound Inhibitor) as a potential upstream regulator of the collagen interactome. This is the first study to detail the collagen types and HYP modifications associated with human AV development and pCAVS. We anticipate that this study will inform new therapeutic avenues that inhibit valvular degradation in pCAVS and engineered options for valve replacement. |
format |
article |
author |
Cassandra L. Clift Yan Ru Su David Bichell Heather C. Jensen Smith Jennifer R. Bethard Kim Norris-Caneda Susana Comte-Walters Lauren E. Ball M. A. Hollingsworth Anand S. Mehta Richard R. Drake Peggi M. Angel |
author_facet |
Cassandra L. Clift Yan Ru Su David Bichell Heather C. Jensen Smith Jennifer R. Bethard Kim Norris-Caneda Susana Comte-Walters Lauren E. Ball M. A. Hollingsworth Anand S. Mehta Richard R. Drake Peggi M. Angel |
author_sort |
Cassandra L. Clift |
title |
Collagen fiber regulation in human pediatric aortic valve development and disease |
title_short |
Collagen fiber regulation in human pediatric aortic valve development and disease |
title_full |
Collagen fiber regulation in human pediatric aortic valve development and disease |
title_fullStr |
Collagen fiber regulation in human pediatric aortic valve development and disease |
title_full_unstemmed |
Collagen fiber regulation in human pediatric aortic valve development and disease |
title_sort |
collagen fiber regulation in human pediatric aortic valve development and disease |
publisher |
Nature Portfolio |
publishDate |
2021 |
url |
https://doaj.org/article/f870ac3e8279454988ad55f7c7a0b959 |
work_keys_str_mv |
AT cassandralclift collagenfiberregulationinhumanpediatricaorticvalvedevelopmentanddisease AT yanrusu collagenfiberregulationinhumanpediatricaorticvalvedevelopmentanddisease AT davidbichell collagenfiberregulationinhumanpediatricaorticvalvedevelopmentanddisease AT heathercjensensmith collagenfiberregulationinhumanpediatricaorticvalvedevelopmentanddisease AT jenniferrbethard collagenfiberregulationinhumanpediatricaorticvalvedevelopmentanddisease AT kimnorriscaneda collagenfiberregulationinhumanpediatricaorticvalvedevelopmentanddisease AT susanacomtewalters collagenfiberregulationinhumanpediatricaorticvalvedevelopmentanddisease AT laureneball collagenfiberregulationinhumanpediatricaorticvalvedevelopmentanddisease AT mahollingsworth collagenfiberregulationinhumanpediatricaorticvalvedevelopmentanddisease AT anandsmehta collagenfiberregulationinhumanpediatricaorticvalvedevelopmentanddisease AT richardrdrake collagenfiberregulationinhumanpediatricaorticvalvedevelopmentanddisease AT peggimangel collagenfiberregulationinhumanpediatricaorticvalvedevelopmentanddisease |
_version_ |
1718391228869902336 |