title: Myeloid-derived growth factor (C19orf10) mediates cardiac repair following myocardial infarction.
abstract: Paracrine-acting proteins are emerging as a central mechanism by which bone marrow cell-based therapies improve tissue repair and heart function after myocardial infarction (MI). We carried out a bioinformatic secretome analysis in bone marrow cells from patients with acute MI to identify novel secreted proteins with therapeutic potential. Functional screens revealed a secreted protein encoded by an open reading frame on chromosome 19 (C19orf10) that promotes cardiac myocyte survival and angiogenesis. We show that bone marrow-derived monocytes and macrophages produce this protein endogenously to protect and repair the heart after MI, and we named it myeloid-derived growth factor (MYDGF). Whereas Mydgf-deficient mice develop larger infarct scars and more severe contractile dysfunction compared to wild-type mice, treatment with recombinant Mydgf reduces scar size and contractile dysfunction after MI. This study is the first to assign a biological function to MYDGF, and it may serve as a prototypical example for the development of protein-based therapies for ischemic tissue repair.
authors.affiliation: 1] Division of Molecular and Translational Cardiology, Hannover Medical School, Hannover, Germany. [2] Department of Cardiology and Angiology, Hannover Medical School, Hannover, Germany.
authors.forename: Mortimer
authors.initials: M
authors.lastname: Korf-Klingebiel
authors.affiliation: 1] Division of Molecular and Translational Cardiology, Hannover Medical School, Hannover, Germany. [2] Department of Cardiology and Angiology, Hannover Medical School, Hannover, Germany.
authors.forename: Marc R
authors.initials: MR
authors.lastname: Reboll
authors.affiliation: 1] Division of Molecular and Translational Cardiology, Hannover Medical School, Hannover, Germany. [2] Department of Cardiology and Angiology, Hannover Medical School, Hannover, Germany.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Klede
authors.affiliation: 1] Division of Molecular and Translational Cardiology, Hannover Medical School, Hannover, Germany. [2] Department of Cardiology and Angiology, Hannover Medical School, Hannover, Germany.
authors.forename: Torben
authors.initials: T
authors.lastname: Brod
authors.affiliation: Core Unit Mass Spectrometry and Proteomics, Institute of Toxicology, Hannover Medical School, Hannover, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Pich
authors.affiliation: Core Unit Mass Spectrometry and Proteomics, Institute of Toxicology, Hannover Medical School, Hannover, Germany.
authors.forename: Felix
authors.initials: F
authors.lastname: Polten
authors.affiliation: Department of Cardiology and Angiology, Hannover Medical School, Hannover, Germany.
authors.forename: L Christian
authors.initials: LC
authors.lastname: Napp
authors.affiliation: Department of Cardiology and Angiology, Hannover Medical School, Hannover, Germany.
authors.forename: Johann
authors.initials: J
authors.lastname: Bauersachs
authors.affiliation: Department of Hematology, Hemostasis, Oncology, and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany.
authors.forename: Arnold
authors.initials: A
authors.lastname: Ganser
authors.affiliation: 1] Division of Molecular and Translational Cardiology, Hannover Medical School, Hannover, Germany. [2] Department of Cardiology and Angiology, Hannover Medical School, Hannover, Germany.
authors.forename: Eva
authors.initials: E
authors.lastname: Brinkmann
authors.affiliation: 1] Division of Molecular and Translational Cardiology, Hannover Medical School, Hannover, Germany. [2] Department of Cardiology and Angiology, Hannover Medical School, Hannover, Germany.
authors.forename: Ines
authors.initials: I
authors.lastname: Reimann
authors.affiliation: 1] Division of Molecular and Translational Cardiology, Hannover Medical School, Hannover, Germany. [2] Department of Cardiology and Angiology, Hannover Medical School, Hannover, Germany.
authors.forename: Tibor
authors.initials: T
authors.lastname: Kempf
authors.affiliation: Department of Pathology and Cardiac Surgery, Institute for Cardiovascular Research, Vrije Universiteit (VU) University Medical Center, Amsterdam, the Netherlands.
authors.forename: Hans W
authors.initials: HW
authors.lastname: Niessen
authors.affiliation: F. Hoffmann-La Roche, Pharma Research and Early Development, Basel, Switzerland.
authors.forename: Jacques
authors.initials: J
authors.lastname: Mizrahi
authors.affiliation: F. Hoffmann-La Roche, Pharma Research and Early Development, Basel, Switzerland.
authors.forename: Hans-Joachim
authors.initials: HJ
authors.lastname: Schönfeld
authors.affiliation: F. Hoffmann-La Roche, Pharma Research and Early Development, Basel, Switzerland.
authors.forename: Antonio
authors.initials: A
authors.lastname: Iglesias
authors.affiliation: F. Hoffmann-La Roche, Pharma Research and Early Development, Basel, Switzerland.
authors.forename: Maria
authors.initials: M
authors.lastname: Bobadilla
authors.affiliation: 1] Division of Molecular and Translational Cardiology, Hannover Medical School, Hannover, Germany. [2] Department of Cardiology and Angiology, Hannover Medical School, Hannover, Germany.
authors.forename: Yong
authors.initials: Y
authors.lastname: Wang
authors.affiliation: 1] Division of Molecular and Translational Cardiology, Hannover Medical School, Hannover, Germany. [2] Department of Cardiology and Angiology, Hannover Medical School, Hannover, Germany.
authors.forename: Kai C
authors.initials: KC
authors.lastname: Wollert
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects / Q000235:genetics; D042783:Endothelial Cells / Q000187:drug effects; D057809:HEK293 Cells; D006801:Humans; D007378:Interleukins / Q000235:genetics* / Q000378:metabolism* / Q000494:pharmacology; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009000:Monocytes / Q000378:metabolism; D009203:Myocardial Infarction / Q000378:metabolism*; D015428:Myocardial Reperfusion Injury / Q000378:metabolism*; D032383:Myocytes, Cardiac; D018919:Neovascularization, Physiologic; D020257:Ventricular Remodeling / Q000187:drug effects / Q000235:genetics
chemical_list: D007378:Interleukins; C464565:MYDGF protein, human; C442281:Mydgf protein, mouse