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Antagonism of stromal cell-derived factor-1alpha reduces infarct size and improves ventricular function after myocardial infarction.

Abstract
To examine the biological impact of locally expressed stromal cell-derived factor-1alpha (SDF-1alpha) during the acute phase of remodeling after myocardial infarction (MI), rats were treated with the selective CXCR4 receptor antagonist AMD3100 (1 mg/kg; given 24 h post-MI and continued for 6 days). In 1-week post-MI rats, intense SDF-1 immunoreactivity was detected in scar-residing vessels, and SDF-1alpha messenger ribonucleic acid (mRNA) levels were significantly greater in the infarct region compared to the noninfarcted left ventricle (NILV). AMD3100 treatment of post-MI rats reduced infarct size, improved systolic function, and partially suppressed the increased expression of atrial natriuretic peptide mRNA in the NILV. The latter finding indirectly suggests that SDF-1alpha may have contributed to the hypertrophic response of the NILV. SDF-1alpha treatment of neonatal rat ventricular myocytes (NNVMs) failed to promote protein synthesis. However, in hypertrophied NNVMs, SDF-1alpha treatment further augmented (3)H-leucine uptake, and AMD3100 selectively inhibited the increase in protein synthesis. Collectively, these data support the existence of an SDF-1alpha gradient in the damaged rat myocardium increasing toward the infarct region and highlight the novel observation that AMD3100 antagonism of the SDF-1alpha/CXCR4 axis reduced scar expansion and improved contractility. In vitro data further suggest that SDF-1alpha may have contributed to the hypertrophic response of the NILV.
AuthorsCindy Proulx, Viviane El-Helou, Hugues Gosselin, Robert Clement, Marc-Antoine Gillis, Louis Villeneuve, Angelino Calderone
JournalPflu╠łgers Archiv : European journal of physiology (Pflugers Arch) Vol. 455 Issue 2 Pg. 241-50 (Nov 2007) ISSN: 0031-6768 [Print] Germany
PMID17520275 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Chemokine CXCL12
  • Cxcr4 protein, rat
  • Heterocyclic Compounds
  • RNA, Messenger
  • Receptors, CXCR4
  • JM 3100
Topics
  • Animals
  • Chemokine CXCL12 (antagonists & inhibitors, metabolism)
  • Disease Models, Animal
  • Heterocyclic Compounds (pharmacology, therapeutic use)
  • Hypertrophy, Left Ventricular (drug therapy, physiopathology)
  • Male
  • Myocardial Infarction (drug therapy, metabolism, pathology)
  • RNA, Messenger (metabolism)
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, CXCR4 (antagonists & inhibitors, physiology)
  • Ventricular Dysfunction, Left (drug therapy, physiopathology)
  • Ventricular Remodeling (physiology)

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