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

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• 作者：Marc-Michael Zaruba ; Hans Diogenes Theiss ; Markus Vallaster ; Ursula Mehl ; Stefan Brunner ; Robert David ; Rebekka Fischer ; Lisa Krieg ; Eva Hirsch ; Bruno Huber ; Petra Nathan ; Lars Israel ; Axel Imhof ; Nadja Herbach ; Gerald Assmann ; Ruediger Wanke ; Josef Mueller-Hoecker ; Gerhard Steinbeck ; Wolfgang-Micha
• 刊名：Cell Stem Cell
• 出版年：2009
• 出版时间：3 April 2009
• 年：2009
• 卷：4
• 期：4
• 页码：313-323
• 全文大小：1542 K

文摘

Summary

Ischemic cardiomyopathy is one of the main causes of death, which may be prevented by stem cell-based therapies. SDF-1α is the major chemokine attracting stem cells to the heart. Since SDF-1α is cleaved and inactivated by CD26/dipeptidylpeptidase IV (DPP-IV), we established a therapeutic concept—applicable 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 posttranslational stabilization of active SDF-1α 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.