title: 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.
authors.affiliation: Département de Physiologie, Université de Montréal, Montréal, QC, Canada.
authors.forename: Cindy
authors.initials: C
authors.lastname: Proulx
authors.forename: Viviane
authors.initials: V
authors.lastname: El-Helou
authors.forename: Hugues
authors.initials: H
authors.lastname: Gosselin
authors.forename: Robert
authors.initials: R
authors.lastname: Clement
authors.forename: Marc-Antoine
authors.initials: MA
authors.lastname: Gillis
authors.forename: Louis
authors.initials: L
authors.lastname: Villeneuve
authors.forename: Angelino
authors.initials: A
authors.lastname: Calderone
mesh_terms: D000818:Animals; D001596:Benzylamines; D054377:Chemokine CXCL12 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000080027:Cyclams; D004195:Disease Models, Animal; D006571:Heterocyclic Compounds / Q000494:pharmacology / Q000627:therapeutic use; D017379:Hypertrophy, Left Ventricular / Q000188:drug therapy / Q000503:physiopathology; D008297:Male; D009203:Myocardial Infarction / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D019718:Receptors, CXCR4 / Q000037:antagonists & inhibitors / Q000502:physiology*; D018487:Ventricular Dysfunction, Left / Q000188:drug therapy / Q000503:physiopathology*; D020257:Ventricular Remodeling / Q000502:physiology
chemical_list: D001596:Benzylamines; D054377:Chemokine CXCL12; C486264:Cxcr4 protein, rat; D000080027:Cyclams; D006571:Heterocyclic Compounds; D012333:RNA, Messenger; D019718:Receptors, CXCR4; C088327:plerixafor