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
  • 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.