Synergy between CD26/DPP-IV Inhibition and G-CSF Improves Cardiac Function after Acute Myocardial Infarction

被引：283

作者：

Zaruba, Marc-Michael ^{[1
]}

Theiss, Hans Diogenes ^{[1
]}

Vallaster, Markus ^{[1
]}

Mehl, Ursula ^{[1
]}

Brunner, Stefan ^{[1
]}

David, Robert ^{[1
]}

Fischer, Rebekka ^{[1
]}

Krieg, Lisa ^{[1
]}

Hirsch, Eva ^{[1
]}

Huber, Bruno ^{[1
]}

Nathan, Petra ^{[1
]}

Israel, Lars ^{[2
,3
]}

Imhof, Axel ^{[2
,3
]}

Herbach, Nadja ^{[4
]}

Assmann, Gerald ^{[5
]}

Wanke, Ruediger ^{[4
]}

Mueller-Hoecker, Josef ^{[5
]}

Steinbeck, Gerhard ^{[1
]}

Franz, Wolfgang-Michael ^{[1
]}

机构：

[1] Univ Munich, Klinikum Grosshadern, Dept Med 1, D-8000 Munich, Germany

[2] Univ Munich, Munich Ctr Integrated Prot Sci, D-8000 Munich, Germany

[3] Univ Munich, Adolf Butenandt Inst, D-8000 Munich, Germany

[4] Univ Munich, Inst Vet Pathol, D-8000 Munich, Germany

[5] Univ Munich, Inst Pathol, D-8000 Munich, Germany

来源：

CELL STEM CELL | 2009年 / 4卷 / 04期

关键词：

STEM-CELL MOBILIZATION; COLONY-STIMULATING FACTOR; DIPEPTIDYL PEPTIDASE IV; BONE-MARROW; HEMATOPOIETIC STEM; PROGENITOR CELLS; CD34(+) CELLS; CD26; SDF-1; CXCL12;

D O I：

10.1016/j.stem.2009.02.013

中图分类号：

Q813 [细胞工程];

学科分类号：

摘要：

Ischemic cardiomyopathy is one of the main causes of death, which may be prevented by stem cell-based therapies. SDF-1 alpha is the major chemokine attracting stem cells to the heart. Since SDF-1 alpha is cleaved and inactivated by CD26/dipeptidylpeptidase IV (DPP-IV), we established a therapeutic conceptapplicable to ischemic disorders in general-by combining genetic and pharmacologic inhibition of DPP-IV with G-CSF-mediated stem cell mobilization after myocardial infarction in mice. This approach leads to (1) decreased myocardial DPP-IV activity, (2) increased myocardial homing of circulating CXCR-4(+) stem cells, (3) reduced cardiac remodeling, and (4) improved heart function and survival. Indeed, CD26 depletion promoted post-translational stabilization of active SDF-1 alpha in heart lysates and preserved the cardiac SDF-1-CXCR4 homing axis. Therefore, we propose pharmacological DPP-IV inhibition and G-CSF-based stem cell mobilization as a therapeutic concept for future stem cell trials after myocardial infarction.

引用

页码：313 / 323

页数：11

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