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.