title: Synergy between CD26/DPP-IV inhibition and G-CSF improves cardiac function after acute myocardial infarction.
abstract: Ischemic cardiomyopathy is one of the main causes of death, which may be prevented by stem cell-based therapies. SDF-1alpha is the major chemokine attracting stem cells to the heart. Since SDF-1alpha 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-1alpha 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.
authors.affiliation: Medical Department I, Klinikum Grosshadern, Ludwig-Maximilians-University, Munich, Germany.
authors.forename: Marc-Michael
authors.initials: MM
authors.lastname: Zaruba
authors.forename: Hans Diogenes
authors.initials: HD
authors.lastname: Theiss
authors.forename: Markus
authors.initials: M
authors.lastname: Vallaster
authors.forename: Ursula
authors.initials: U
authors.lastname: Mehl
authors.forename: Stefan
authors.initials: S
authors.lastname: Brunner
authors.forename: Robert
authors.initials: R
authors.lastname: David
authors.forename: Rebekka
authors.initials: R
authors.lastname: Fischer
authors.forename: Lisa
authors.initials: L
authors.lastname: Krieg
authors.forename: Eva
authors.initials: E
authors.lastname: Hirsch
authors.forename: Bruno
authors.initials: B
authors.lastname: Huber
authors.forename: Petra
authors.initials: P
authors.lastname: Nathan
authors.forename: Lars
authors.initials: L
authors.lastname: Israel
authors.forename: Axel
authors.initials: A
authors.lastname: Imhof
authors.forename: Nadja
authors.initials: N
authors.lastname: Herbach
authors.forename: Gerald
authors.initials: G
authors.lastname: Assmann
authors.forename: Ruediger
authors.initials: R
authors.lastname: Wanke
authors.forename: Josef
authors.initials: J
authors.lastname: Mueller-Hoecker
authors.forename: Gerhard
authors.initials: G
authors.lastname: Steinbeck
authors.forename: Wolfgang-Michael
authors.initials: WM
authors.lastname: Franz