Proulx Cindy, El-Helou Viviane, Gosselin Hugues, Clement Robert, Gillis Marc-Antoine, Villeneuve Louis, Calderone Angelino
Département de Physiologie, Université de Montréal, Montréal, QC, Canada.
Pflugers Arch. 2007 Nov;455(2):241-50. doi: 10.1007/s00424-007-0284-5. Epub 2007 May 23.
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.
为了研究心肌梗死（MI）后重塑急性期局部表达的基质细胞衍生因子-1α（SDF-1α）的生物学影响，对大鼠给予选择性CXCR4受体拮抗剂AMD3100（1 mg/kg；MI后24小时给药并持续6天）。在MI后1周的大鼠中，在瘢痕中的血管中检测到强烈的SDF-1免疫反应性，与未梗死的左心室（NILV）相比，梗死区域的SDF-1α信使核糖核酸（mRNA）水平显著更高。对MI后大鼠进行AMD3100治疗可减小梗死面积，改善收缩功能，并部分抑制NILV中利钠肽mRNA表达的增加。后一发现间接表明SDF-1α可能促成了NILV的肥大反应。用SDF-1α处理新生大鼠心室肌细胞（NNVMs）未能促进蛋白质合成。然而，在肥大的NNVMs中，SDF-1α处理进一步增加了（3）H-亮氨酸摄取，而AMD3100选择性抑制了蛋白质合成的增加。总体而言，这些数据支持在受损大鼠心肌中存在朝向梗死区域增加的SDF-1α梯度，并突出了新的观察结果，即AMD3100对SDF-1α/CXCR4轴的拮抗作用减少了瘢痕扩展并改善了收缩性。体外数据进一步表明SDF-1α可能促成了NILV的肥大反应。
