Division of Cardio-Vascular Medicine, Department of Medicine, Kurume University School of Medicine, Kurume, Japan.
Am J Pathol. 2011 Feb;178(2):591-8. doi: 10.1016/j.ajpath.2010.10.018.
Oxidative stress and inflammation are involved in cardiac remodeling after acute myocardial infarction (AMI). We have found that pigment epithelium-derived factor (PEDF) inhibits vascular inflammation through its anti-oxidative properties. However, effects of PEDF on cardiac remodeling after AMI remain unknown. We investigated whether PEDF could inhibit left ventricular remodeling and improve cardiac function in rats with AMI. AMI was induced in 8-week-old Sprague-Dawley rats by ligation of the left ascending coronary artery. Rats were treated intravenously with vehicle or 10 μg PEDF/100 g b.wt. every day for up to 2 weeks after AMI. Each rat was followed until 16 weeks of age. PEDF levels in infarcted areas and serum were significantly decreased at 1 week after AMI and remained low during the observational periods. PEDF administration inhibited apoptotic cell death and oxidative stress generation around the infarcted areas at 2 and 8 weeks after AMI. Further, PEDF injection suppressed cardiac fibrosis by reducing transforming growth factor-β and type III collagen expression, improved left ventricular ejection fraction, ameliorated diastolic dysfunction, and inhibited the increase in left ventricular mass index at 8 weeks after AMI. The present study demonstrated that PEDF could inhibit tissue remodeling and improve cardiac function in AMI rats. Substitution of PEDF may be a novel therapeutic strategy for cardiac remodeling after AMI.
氧化应激和炎症参与急性心肌梗死（AMI）后的心脏重构。我们已经发现，色素上皮衍生因子（PEDF）通过其抗氧化特性抑制血管炎症。然而，PEDF 对 AMI 后心脏重构的影响尚不清楚。我们研究了 PEDF 是否可以抑制 AMI 大鼠的左心室重构并改善心脏功能。通过结扎左冠状动脉升支在 8 周龄 Sprague-Dawley 大鼠中诱导 AMI。AMI 后，大鼠每天静脉注射载体或 10μg PEDF/100g b.wt.，持续 2 周以上。每只大鼠随访至 16 周龄。AMI 后 1 周，梗死区和血清中 PEDF 水平显著降低，观察期间一直较低。PEDF 给药可抑制 AMI 后 2 周和 8 周梗死区周围的细胞凋亡和氧化应激生成。此外，PEDF 注射通过减少转化生长因子-β和 III 型胶原的表达抑制心肌纤维化，改善左心室射血分数，改善舒张功能，并抑制 AMI 后 8 周左心室质量指数的增加。本研究表明，PEDF 可抑制 AMI 大鼠的组织重构并改善心脏功能。PEDF 的替代可能是 AMI 后心脏重构的一种新的治疗策略。
