Department of Cardiovascular Sciences, KU Leuven, Herestraat 49, 3000, Leuven, Belgium.
CoBioRes, NV, Leuven, Belgium.
J Cardiovasc Transl Res. 2017 Aug;10(4):348-358. doi: 10.1007/s12265-017-9742-4. Epub 2017 Apr 10.
Angiogenic growth factor therapy for ischemic cardiovascular disease carries a risk of stimulating atherosclerotic plaque growth. We evaluated risk benefit ratio of sustained administration of recombinant human placental growth factor (rhPlGF)-2 in mice with advanced atherosclerosis and chronic ischemic cardiomyopathy. We maintained apolipoprotein E-deficient mice on a high cholesterol diet and induced myocardial infarction by transient ligation at 4 weeks. At 8 weeks, we assessed left ventricular (LV) function and randomized mice to receive rhPlGF-2 or vehicle (VEH) subcutaneously for 28 days. Administration of rhPlGF-2 significantly increased PlGF plasma levels without adverse hemodynamic or systemic inflammatory effects. RhPlGF-2 did not increase plaque area, composition, or vulnerability in the aortic arch. RhPlGF-2 significantly improved contractile function and reduced LV end-systolic and end-diastolic volume indices with a concomitant increase in capillary and arteriolar density in ischemic myocardium. RhPlGF-2 may represent a promising therapeutic strategy in chronic ischemic cardiomyopathy.
血管生成生长因子治疗缺血性心血管疾病存在刺激动脉粥样硬化斑块生长的风险。我们评估了持续给予重组人胎盘生长因子（rhPlGF-2）在患有晚期动脉粥样硬化和慢性缺血性心肌病的小鼠中的风险效益比。我们让载脂蛋白 E 缺陷型小鼠食用高胆固醇饮食，并在 4 周时通过短暂结扎诱导心肌梗死。在 8 周时，我们评估了左心室（LV）功能，并将小鼠随机分为接受 rhPlGF-2 或载体（VEH）皮下注射 28 天的治疗组。rhPlGF-2 的给药显著增加了 PlGF 的血浆水平，而没有不良的血液动力学或全身炎症反应。rhPlGF-2 没有增加主动脉弓中的斑块面积、组成或易损性。rhPlGF-2 显著改善了收缩功能，减少了 LV 收缩末期和舒张末期容积指数，同时增加了缺血心肌中的毛细血管和小动脉密度。rhPlGF-2 可能是慢性缺血性心肌病的一种有前途的治疗策略。
