dc.contributor.author
Yang, Jin
dc.contributor.author
Savvatis, Konstantinos
dc.contributor.author
Kang, Jong Seok
dc.contributor.author
Fan, Peidong
dc.contributor.author
Zhong, Hongyan
dc.contributor.author
Schwartz, Karen
dc.contributor.author
Barry, Vivian
dc.contributor.author
Kasner, Mario
dc.contributor.author
Tschoepe, Carsten [u.v.m.]
dc.date.accessioned
2018-06-08T11:02:23Z
dc.date.available
2017-02-01T12:12:34.240Z
dc.identifier.uri
https://refubium.fu-berlin.de/handle/fub188/21499
dc.identifier.uri
http://dx.doi.org/10.17169/refubium-24791
dc.description.abstract
Interstitial fibrosis plays a key role in the development and progression of
heart failure. Here, we show that an enzyme that crosslinks collagen—Lysyl
oxidase-like 2 (Loxl2)—is essential for interstitial fibrosis and mechanical
dysfunction of pathologically stressed hearts. In mice, cardiac stress
activates fibroblasts to express and secrete Loxl2 into the interstitium,
triggering fibrosis, systolic and diastolic dysfunction of stressed hearts.
Antibody-mediated inhibition or genetic disruption of Loxl2 greatly reduces
stress-induced cardiac fibrosis and chamber dilatation, improving systolic and
diastolic functions. Loxl2 stimulates cardiac fibroblasts through PI3K/AKT to
produce TGF-β2, promoting fibroblast-to-myofibroblast transformation; Loxl2
also acts downstream of TGF-β2 to stimulate myofibroblast migration. In
diseased human hearts, LOXL2 is upregulated in cardiac interstitium; its
levels correlate with collagen crosslinking and cardiac dysfunction. LOXL2 is
also elevated in the serum of heart failure (HF) patients, correlating with
other HF biomarkers, suggesting a conserved LOXL2-mediated mechanism of human
HF.
en
dc.rights.uri
http://creativecommons.org/licenses/by/4.0/
dc.subject
Preclinical research
dc.subject.ddc
600 Technik, Medizin, angewandte Wissenschaften::610 Medizin und Gesundheit
dc.title
Targeting LOXL2 for cardiac interstitial fibrosis and heart failure treatment
dc.type
Wissenschaftlicher Artikel
dcterms.bibliographicCitation
Nature Communications. - 7 (2016), Artikel Nr. 13710
dcterms.bibliographicCitation.doi
10.1038/ncomms13710
dcterms.bibliographicCitation.url
http://www.nature.com/articles/ncomms13710
refubium.affiliation
Charité - Universitätsmedizin Berlin
de
refubium.mycore.fudocsId
FUDOCS_document_000000026237
refubium.note.author
Der Artikel wurde in einer reinen Open-Access-Zeitschrift publiziert.
refubium.resourceType.isindependentpub
no
refubium.mycore.derivateId
FUDOCS_derivate_000000007608
dcterms.accessRights.openaire
open access