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Stromal cell-derived factor-1 retention and cardioprotection for ischemic myocardium

Sachiko Kanki, Vincent FM Segers, WeiTao Wu, Rahul Kakkar, Joseph Gannon, Stanislas Sys UGent, Anthony Sandrasagra and Richard T Lee (2011) CIRCULATION-HEART FAILURE. 4(4).
abstract
Background-Stromal cell-derived factor-1 (SDF-1) is a chemoattractant of stem/progenitor cells, and several studies have shown that SDF-1 may improve ventricular function after infarction. SDF-1 is cleaved by proteases including matrix metalloproteinase-2 (MMP-2) and CD26/dipeptidylpeptidase-4 (DPP-4), which are activated in injured tissues. Methods and Results-We investigated the biodistribution and functional roles of SDF-1 in experimental ischemia/reperfusion injury in rats. Radiolabeled SDF-1 given by intracoronary injection was selectively concentrated in ischemic myocardium. The enhanced uptake of SDF-1 in ischemic myocardium was not mediated by its receptor, CXCR4. Mass spectrometry and Western analyses showed that SDF-1 was cleaved by DPP-4 in plasma and myocardium, whereas a bioengineered MMP-2/DPP-4-resistant form of SDF-1, SSDF-1(S4V), was highly stable. A single dose of SSDF1(S4V) exhibited greater potency for cardioprotection than wild-type SDF-1. SSDF-1(S4V) improved cardiac function in rats even after a 3-hour ischemic period. Conclusions-These results show that a single dose of protease-resistant SSDF-1(S4V) after myocardial infarction leads to dramatic improvement in angiogenesis and ventricular function even 3 hours after the onset of ischemia, revealing a simple, clinically feasible approach to prevention of heart failure.
Please use this url to cite or link to this publication:
author
organization
year
type
journalArticle (original)
publication status
published
subject
keyword
heart failure, CHEMOKINE RECEPTOR CXCR4, reperfusion, angiogenesis, cardioprotection, ischemia, myocardium, EXPRESSION, HEART-FAILURE, INFARCTION, FACTOR-1-ALPHA, SDF-1, MICE, CARDIOMYOPATHY, LYMPHOPOIESIS, MYELOPOIESIS
journal title
CIRCULATION-HEART FAILURE
Circ.-Heart Fail.
volume
4
issue
4
pages
20 pages
Web of Science type
Article
Web of Science id
000292871300017
JCR category
CARDIAC & CARDIOVASCULAR SYSTEMS
JCR impact factor
6.286 (2011)
JCR rank
11/117 (2011)
JCR quartile
1 (2011)
ISSN
1941-3289
DOI
10.1161/CIRCHEARTFAILURE.110.960302
language
English
UGent publication?
yes
classification
A1
copyright statement
I have transferred the copyright for this publication to the publisher
id
1988514
handle
http://hdl.handle.net/1854/LU-1988514
date created
2012-01-17 09:15:32
date last changed
2016-12-19 15:42:53
@article{1988514,
  abstract     = {Background-Stromal cell-derived factor-1 (SDF-1) is a chemoattractant of stem/progenitor cells, and several studies have shown that SDF-1 may improve ventricular function after infarction. SDF-1 is cleaved by proteases including matrix metalloproteinase-2 (MMP-2) and CD26/dipeptidylpeptidase-4 (DPP-4), which are activated in injured tissues. 
Methods and Results-We investigated the biodistribution and functional roles of SDF-1 in experimental ischemia/reperfusion injury in rats. Radiolabeled SDF-1 given by intracoronary injection was selectively concentrated in ischemic myocardium. The enhanced uptake of SDF-1 in ischemic myocardium was not mediated by its receptor, CXCR4. Mass spectrometry and Western analyses showed that SDF-1 was cleaved by DPP-4 in plasma and myocardium, whereas a bioengineered MMP-2/DPP-4-resistant form of SDF-1, SSDF-1(S4V), was highly stable. A single dose of SSDF1(S4V) exhibited greater potency for cardioprotection than wild-type SDF-1. SSDF-1(S4V) improved cardiac function in rats even after a 3-hour ischemic period. 
Conclusions-These results show that a single dose of protease-resistant SSDF-1(S4V) after myocardial infarction leads to dramatic improvement in angiogenesis and ventricular function even 3 hours after the onset of ischemia, revealing a simple, clinically feasible approach to prevention of heart failure.},
  author       = {Kanki, Sachiko and Segers, Vincent FM and Wu, WeiTao and Kakkar, Rahul and Gannon, Joseph and Sys, Stanislas and Sandrasagra, Anthony and Lee, Richard T},
  issn         = {1941-3289},
  journal      = {CIRCULATION-HEART FAILURE},
  keyword      = {heart failure,CHEMOKINE RECEPTOR CXCR4,reperfusion,angiogenesis,cardioprotection,ischemia,myocardium,EXPRESSION,HEART-FAILURE,INFARCTION,FACTOR-1-ALPHA,SDF-1,MICE,CARDIOMYOPATHY,LYMPHOPOIESIS,MYELOPOIESIS},
  language     = {eng},
  number       = {4},
  pages        = {20},
  title        = {Stromal cell-derived factor-1 retention and cardioprotection for ischemic myocardium},
  url          = {http://dx.doi.org/10.1161/CIRCHEARTFAILURE.110.960302},
  volume       = {4},
  year         = {2011},
}

Chicago
Kanki, Sachiko, Vincent FM Segers, WeiTao Wu, Rahul Kakkar, Joseph Gannon, Stanislas Sys, Anthony Sandrasagra, and Richard T Lee. 2011. “Stromal Cell-derived Factor-1 Retention and Cardioprotection for Ischemic Myocardium.” Circulation-heart Failure 4 (4).
APA
Kanki, S., Segers, V. F., Wu, W., Kakkar, R., Gannon, J., Sys, S., Sandrasagra, A., et al. (2011). Stromal cell-derived factor-1 retention and cardioprotection for ischemic myocardium. CIRCULATION-HEART FAILURE, 4(4).
Vancouver
1.
Kanki S, Segers VF, Wu W, Kakkar R, Gannon J, Sys S, et al. Stromal cell-derived factor-1 retention and cardioprotection for ischemic myocardium. CIRCULATION-HEART FAILURE. 2011;4(4).
MLA
Kanki, Sachiko, Vincent FM Segers, WeiTao Wu, et al. “Stromal Cell-derived Factor-1 Retention and Cardioprotection for Ischemic Myocardium.” CIRCULATION-HEART FAILURE 4.4 (2011): n. pag. Print.