Therapies that target scar formation after myocardial infarction (MI) could prevent ensuing heart failure or death from ventricular arrhythmias. We have previously shown that recombinant human platelet-derived growth factor-AB (rhPDGF-AB) improves cardiac function in a rodent model of MI. To progress clinical translation, we evaluated rhPDGF-AB treatment in a clinically relevant porcine model of myocardial ischemia-reperfusion. Thirty-six pigs were randomized to sham procedure or balloon occlusion of the proximal left anterior descending coronary artery with 7-day intravenous infusion of rhPDGF-AB or vehicle. One month after MI, rhPDGF-AB improved survival by 40% compared with vehicle, and cardiac magnetic resonance imaging showed left ventricular (LV) ejection fraction improved by 11.5%, driven by reduced LV end-systolic volumes. Pressure volume loop analyses revealed improved myocardial contractility and energetics after rhPDGF-AB treatment with minimal effect on ventricular compliance. rhPDGF-AB enhanced angiogenesis and increased scar anisotropy (high fiber alignment) without affecting overall scar size or stiffness. rhPDGF-AB reduced inducible ventricular tachycardia by decreasing heterogeneity of the ventricular scar that provides a substrate for reentrant circuits. In summary, we demonstrated that rhPDGF-AB promotes post-MI cardiac wound repair by altering the mechanics of the infarct scar, resulting in robust cardiac functional improvement, decreased ventricular arrhythmias, and improved survival. Our findings suggest a strong translational potential for rhPDGF-AB as an adjunct to current MI treatment and possibly to modulate scar in other organs.

中文翻译：

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血小板衍生的生长因子-AB可改善心肌梗死后的疤痕力学和血管性。

针对心肌梗塞（MI）后疤痕形成的治疗方法可以防止随后发生的心力衰竭或室性心律失常导致的死亡。先前我们已经表明，重组人血小板源性生长因子-AB（rhPDGF-AB）可以改善MI啮齿动物模型的心脏功能。为了进行临床翻译，我们在临床相关的猪心肌缺血-再灌注模型中评估了rhPDGF-AB的治疗。三十六头猪被随机分配至假手术或冠状动脉闭塞的左前降支近端用球囊闭塞术，并经7天静脉内注射rhPDGF-AB或溶媒。心肌梗死一个月后，rhPDGF-AB的存活率比媒介物提高了40％，心脏磁共振成像显示左心室（LV）射血分数提高了11.5％，这是由于LV收缩末期容积减少所致。压力容积环分析显示，rhPDGF-AB治疗后改善了心肌收缩力和能量，对心室顺应性影响最小。rhPDGF-AB可增强血管生成并增加疤痕各向异性（高纤维排列），而不会影响整体疤痕的大小或硬度。rhPDGF-AB通过减少心室瘢痕的异质性减少可诱导的室性心动过速，该异质性为折返回路提供了底物。总而言之，我们证明了rhPDGF-AB通过改变梗塞疤痕的机制来促进MI后心脏伤口的修复，从而导致心脏功能的显着改善，室性心律失常的减少以及存活率的提高。我们的发现表明，rhPDGF-AB具有强大的翻译潜力，可作为当前心梗治疗的辅助手段，并可能调节其他器官的瘢痕。