Cysteine-rich with EGF-like domains 2 (CRELD2) is an endoplasmic reticulum stress-inducible angiogenic growth factor promoting ischemic heart repair.
Animals
Endoplasmic Reticulum Stress
/ drug effects
Humans
Neovascularization, Physiologic
/ drug effects
Mice, Inbred C57BL
Disease Models, Animal
Endothelial Cells
/ metabolism
Mice, Knockout
Myocardial Infarction
/ metabolism
Male
Cells, Cultured
Signal Transduction
/ drug effects
Mice
Angiogenesis Inducing Agents
/ pharmacology
Journal
Nature cardiovascular research
ISSN: 2731-0590
Titre abrégé: Nat Cardiovasc Res
Pays: England
ID NLM: 9918284280206676
Informations de publication
Date de publication:
Feb 2024
Feb 2024
Historique:
received:
28
06
2023
accepted:
07
12
2023
medline:
28
8
2024
pubmed:
28
8
2024
entrez:
28
8
2024
Statut:
ppublish
Résumé
Tissue repair after myocardial infarction (MI) is guided by autocrine and paracrine-acting proteins. Deciphering these signals and their upstream triggers is essential when considering infarct healing as a therapeutic target. Here we perform a bioinformatic secretome analysis in mouse cardiac endothelial cells and identify cysteine-rich with EGF-like domains 2 (CRELD2), an endoplasmic reticulum stress-inducible protein with poorly characterized function. CRELD2 was abundantly expressed and secreted in the heart after MI in mice and patients. Creld2-deficient mice and wild-type mice treated with a CRELD2-neutralizing antibody showed impaired de novo microvessel formation in the infarct border zone and developed severe postinfarction heart failure. CRELD2 protein therapy, conversely, improved heart function after MI. Exposing human coronary artery endothelial cells to recombinant CRELD2 induced angiogenesis, associated with a distinct phosphoproteome signature. These findings identify CRELD2 as an angiogenic growth factor and unravel a link between endoplasmic reticulum stress and ischemic tissue repair.
Identifiants
pubmed: 39196188
doi: 10.1038/s44161-023-00411-x
pii: 10.1038/s44161-023-00411-x
doi:
Substances chimiques
Angiogenesis Inducing Agents
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
186-202Subventions
Organisme : Deutsche Forschungsgemeinschaft (German Research Foundation)
ID : WO 552/12-1
Organisme : Niedersächsisches Ministerium für Wissenschaft und Kultur (Ministry for Science and Culture of Lower Saxony)
ID : VW-ZN3440
Informations de copyright
© 2024. The Author(s).
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