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

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.