Authors: Cindy Proulx Viviane ElHelou Hugues Gosselin Robert Clement MarcAntoine Gillis Louis Villeneuve Angelino Calderone
Publish Date: 2007/05/23
Volume: 455, Issue: 2, Pages: 241-250
Abstract
To examine the biological impact of locally expressed stromal cellderived factor1α SDF1α 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 postMI and continued for 6 days In 1week postMI rats intense SDF1 immunoreactivity was detected in scarresiding vessels and SDF1α messenger ribonucleic acid mRNA levels were significantly greater in the infarct region compared to the noninfarcted left ventricle NILV AMD3100 treatment of postMI 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 SDF1α may have contributed to the hypertrophic response of the NILV SDF1α treatment of neonatal rat ventricular myocytes NNVMs failed to promote protein synthesis However in hypertrophied NNVMs SDF1α treatment further augmented 3Hleucine uptake and AMD3100 selectively inhibited the increase in protein synthesis Collectively these data support the existence of an SDF1α gradient in the damaged rat myocardium increasing toward the infarct region and highlight the novel observation that AMD3100 antagonism of the SDF1α/CXCR4 axis reduced scar expansion and improved contractility In vitro data further suggest that SDF1α may have contributed to the hypertrophic response of the NILVThis work was supported by the Heart and Stroke Foundation of Canada and Quebec Canadian Institutes of Health Research and “La Fondation de l’Institut de Cardiologie de Montréal” Dr Calderone is a “Chercheur–Boursier National du Fonds de la recherche en santé du Québec” I would like to thank France Thériault for excellent secretarial assistance Cindy Proulx and Viviane ElHelou contributed equally to the study
Keywords: