dc.contributor.author
Hiepen, Christian
dc.contributor.author
Jatzlau, Jerome
dc.contributor.author
Knaus, Petra
dc.date.accessioned
2021-01-22T12:25:08Z
dc.date.available
2021-01-22T12:25:08Z
dc.identifier.uri
https://refubium.fu-berlin.de/handle/fub188/29331
dc.identifier.uri
http://dx.doi.org/10.17169/refubium-29077
dc.description.abstract
Cardiovascular disorders are still the leading cause for mortality in the western world and challenge economies with steadily increasing healthcare costs. Understanding the precise molecular pathomechanisms behind and identifying players involved in the early onset of cardiovascular diseases remains crucial for the development of new therapeutic strategies. Taking advantage of CRISPR/Cas9 gene editing in human endothelial cells (ECs), we re-investigated the early molecular steps in a genetic vascular disorder termed pulmonary arterial hypertension (PAH) in our recent study (Hiepen C., Jatzlau J. et al.; PLOS Biol, 2019). Here, mutations in the Bone Morphogenetic Protein type II receptor (BMPR2) prime for the hereditary form (HPAH) with downregulated BMPR2 followed by a characteristic change in SMAD signaling, i.e. gain in both SMAD1/5 and SMAD2/3 responses. Remarkably these cells show increased susceptibility to signaling by TGFβ due to remodeling of the extracellular matrix (ECM) and increased biomechanics acting as a secondary stressor for ECs pathobiology. This clearly places BMPR2 not only as a BMP-signaling receptor, but also as a gatekeeper to protect ECs from excess TGFβ signaling.
en
dc.format.extent
4 Seiten
dc.rights.uri
https://creativecommons.org/licenses/by/4.0/
dc.subject.ddc
500 Naturwissenschaften und Mathematik::570 Biowissenschaften; Biologie::570 Biowissenschaften; Biologie
dc.title
Biomechanical stress provides a second hit in the establishment of BMP/TGFβ-related vascular disorders
dc.type
Wissenschaftlicher Artikel
dcterms.bibliographicCitation.doi
10.1371/journal.pbio.3000557
dcterms.bibliographicCitation.journaltitle
Cell Stress
dcterms.bibliographicCitation.number
2
dcterms.bibliographicCitation.pagestart
44
dcterms.bibliographicCitation.pageend
47
dcterms.bibliographicCitation.volume
4
dcterms.bibliographicCitation.url
https://doi.org/10.1371/journal.pbio.3000557
refubium.affiliation
Biologie, Chemie, Pharmazie
refubium.affiliation.other
Institut für Chemie und Biochemie

refubium.resourceType.isindependentpub
no
dcterms.accessRights.openaire
open access
dcterms.isPartOf.eissn
2523-0204
refubium.resourceType.provider
WoS-Alert