Cysteine-rich with EGF-like domains 2 (CRELD2) is an endoplasmic reticulum stress-inducible angiogenic growth factor promoting ischemic heart repair.

Autor: Wu X; Division of Molecular and Translational Cardiology, Hans Borst Center for Heart and Stem Cell Research, Hannover Medical School, Hannover, Germany.; Department of Cardiology and Angiology, Hannover Medical School, Hannover, Germany.; Stanford University School of Medicine, Stanford, CA, USA., Zheng L; Division of Molecular and Translational Cardiology, Hans Borst Center for Heart and Stem Cell Research, Hannover Medical School, Hannover, Germany.; Department of Cardiology and Angiology, Hannover Medical School, Hannover, Germany.; Department of Cardiology, Shanghai General Hospital, Shanghai, China., Reboll MR; Division of Molecular and Translational Cardiology, Hans Borst Center for Heart and Stem Cell Research, Hannover Medical School, Hannover, Germany.; Department of Cardiology and Angiology, Hannover Medical School, Hannover, Germany., Hyde LF; Division of Molecular and Translational Cardiology, Hans Borst Center for Heart and Stem Cell Research, Hannover Medical School, Hannover, Germany.; Department of Cardiology and Angiology, Hannover Medical School, Hannover, Germany., Mass E; Developmental Biology of the Immune System, Life & Medical Sciences Institute, University of Bonn, Bonn, Germany., Niessen HW; Department of Pathology and Department of Cardiac Surgery, Institute for Cardiovascular Research, Amsterdam University Medical Center, Amsterdam, The Netherlands., Kosanke M; Research Core Unit Genomics, Hannover Medical School, Hannover, Germany., Pich A; Core Unit Proteomics and Institute of Toxicology, Hannover Medical School, Hannover, Germany., Giannitsis E; Department of Medicine III, Heidelberg University, Heidelberg, Germany., Tillmanns J; Department of Cardiology and Angiology, Hannover Medical School, Hannover, Germany., Bauersachs J; Department of Cardiology and Angiology, Hannover Medical School, Hannover, Germany., Heineke J; Department of Cardiology and Angiology, Hannover Medical School, Hannover, Germany.; Department of Cardiovascular Physiology, European Center for Angioscience, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany., Wang Y; Division of Molecular and Translational Cardiology, Hans Borst Center for Heart and Stem Cell Research, Hannover Medical School, Hannover, Germany.; Department of Cardiology and Angiology, Hannover Medical School, Hannover, Germany., Korf-Klingebiel M; Division of Molecular and Translational Cardiology, Hans Borst Center for Heart and Stem Cell Research, Hannover Medical School, Hannover, Germany.; Department of Cardiology and Angiology, Hannover Medical School, Hannover, Germany., Polten F; Division of Molecular and Translational Cardiology, Hans Borst Center for Heart and Stem Cell Research, Hannover Medical School, Hannover, Germany.; Department of Cardiology and Angiology, Hannover Medical School, Hannover, Germany., Wollert KC; Division of Molecular and Translational Cardiology, Hans Borst Center for Heart and Stem Cell Research, Hannover Medical School, Hannover, Germany. wollert.kai@mh-hannover.de.; Department of Cardiology and Angiology, Hannover Medical School, Hannover, Germany. wollert.kai@mh-hannover.de.
Jazyk: angličtina
Zdroj: Nature cardiovascular research [Nat Cardiovasc Res] 2024 Feb; Vol. 3 (2), pp. 186-202. Date of Electronic Publication: 2024 Jan 17.
DOI: 10.1038/s44161-023-00411-x
Abstrakt: 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.
(© 2024. The Author(s).)
Databáze: MEDLINE
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