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

被引：214

作者：

Korf-Klingebiel, Mortimer ^{[1
,2
]}

Reboll, Marc R. ^{[1
,2
]}

Klede, Stefanie ^{[1
,2
]}

Brod, Torben ^{[1
,2
]}

Pich, Andreas ^{[3
]}

Polten, Felix ^{[3
]}

Napp, L. Christian ^{[2
]}

Bauersachs, Johann ^{[2
]}

Ganser, Arnold ^{[4
]}

Brinkmann, Eva ^{[1
,2
]}

Reimann, Ines ^{[1
,2
]}

Kempf, Tibor ^{[1
,2
]}

Niessen, Hans W. ^{[5
]}

Mizrahi, Jacques ^{[6
]}

Schoenfeld, Hans-Joachim ^{[6
]}

Iglesias, Antonio ^{[6
]}

Bobadilla, Maria ^{[6
]}

Wang, Yong ^{[1
,2
]}

Wollert, Kai C. ^{[1
,2
]}

机构：

[1] Hannover Med Sch, Div Mol & Translat Cardiol, Hannover, Germany

[2] Hannover Med Sch, Dept Cardiol & Angiol, Hannover, Germany

[3] Hannover Med Sch, Inst Toxicol, Core Unit Mass Spectrometry & Prote, Hannover, Germany

[4] Hannover Med Sch, Dept Hematol Hemostasis Oncol & Stem Cell Transpl, Hannover, Germany

[5] Vrije Univ Amsterdam, Univ Med Ctr, Inst Cardiovasc Res, Dept Pathol & Cardiac Surg, Amsterdam, Netherlands

[6] F Hoffmann La Roche, Pharma Res & Early Dev, Basel, Switzerland

来源：

NATURE MEDICINE | 2015年 / 21卷 / 02期

关键词：

CELL THERAPY; MONONUCLEAR-CELLS; HEART-DISEASE; PROTEIN; IDENTIFICATION; ACTIVATION; MONOCYTES; SECRETOME; EFFICACY; IMPAIRS;

D O I：

10.1038/nm.3778

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

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.

引用

页码：140 / 149

页数：10

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