2. Academic Validation
  3. Myeloid-derived growth factor (C19orf10) mediates cardiac repair following myocardial infarction

Myeloid-derived growth factor (C19orf10) mediates cardiac repair following myocardial infarction

  • Nat Med. 2015 Feb;21(2):140-9. doi: 10.1038/nm.3778.
Mortimer Korf-Klingebiel 1,  Marc R Reboll 1,  Stefanie Klede 1,  Torben Brod 1,  Andreas Pich 2,  Felix Polten 2,  L Christian Napp 3,  Johann Bauersachs 3,  Arnold Ganser 4,  Eva Brinkmann 1,  Ines Reimann 1,  Tibor Kempf 1,  Hans W Niessen 5,  Jacques Mizrahi 6,  Hans-Joachim Schönfeld 6,  Antonio Iglesias 6,  Maria Bobadilla 6,  Yong Wang 1,  Kai C Wollert 1
Affiliations

Affiliations

  • 1 1] Division of Molecular and Translational Cardiology, Hannover Medical School, Hannover, Germany. [2] Department of Cardiology and Angiology, Hannover Medical School, Hannover, Germany.
  • 2 Core Unit Mass Spectrometry and Proteomics, Institute of Toxicology, Hannover Medical School, Hannover, Germany.
  • 3 Department of Cardiology and Angiology, Hannover Medical School, Hannover, Germany.
  • 4 Department of Hematology, Hemostasis, Oncology, and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany.
  • 5 Department of Pathology and Cardiac Surgery, Institute for Cardiovascular Research, Vrije Universiteit (VU) University Medical Center, Amsterdam, the Netherlands.
  • 6 F. Hoffmann-La Roche, Pharma Research and Early Development, Basel, Switzerland.
PMID: 25581518 DOI: 10.1038/nm.3778
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.

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