Khurana Rohit, Moons Lieve, Shafi Shahida, Luttun Aernout, Collen Désiré, Martin John F, Carmeliet Peter, Zachary Ian C
BHF Laboratories, Department of Medicine, University College London, 5 University St, London WC1E 6JJ, United Kingdom.
Circulation. 2005 May 31;111(21):2828-36. doi: 10.1161/CIRCULATIONAHA.104.495887. Epub 2005 May 23.
Placental growth factor (PlGF) has been implicated in the pathophysiological angiogenesis and monocyte recruitment that underlie chronic inflammatory disease, but its role in atherosclerosis has not been examined. We investigated the effects of exogenous PlGF, delivered by adenoviral gene transfer, on atherogenic intimal thickening and macrophage accumulation induced by collar placement around the rabbit carotid artery and examined the effects of PlGF deficiency on atherosclerosis in apolipoprotein E-deficient (apoE(-/-)) mice.
Periadventitial transfer of PlGF2-encoding adenoviruses significantly increased intimal thickening, macrophage accumulation, endothelial vascular cell adhesion molecule-1 expression, and adventitial neovascularization in the collared arteries of hypercholesterolemic rabbits and increased the intima-to-media ratio in rabbits fed a normal diet. Neointimal macrophages were associated with increased expression of the PlGF receptor Flt-1. The size and macrophage content of early atherosclerotic lesions were reduced in mice deficient in both apoE and PlGF compared with apoE-deficient mice.
Local adenoviral PlGF2 delivery promotes atherogenic neointima formation in hypercholesterolemic rabbits, and PlGF is required for macrophage infiltration in early atherosclerotic lesions in apoE(-/-) mice. These findings support a novel role for PlGF in the pathogenesis of atherosclerotic disease.
胎盘生长因子（PlGF）与慢性炎症性疾病所涉及的病理生理血管生成和单核细胞募集有关，但其在动脉粥样硬化中的作用尚未得到研究。我们研究了通过腺病毒基因转移递送的外源性PlGF对兔颈动脉周围放置颈圈诱导的动脉粥样硬化内膜增厚和巨噬细胞积聚的影响，并研究了PlGF缺乏对载脂蛋白E缺陷（apoE(-/-)）小鼠动脉粥样硬化的影响。
编码PlGF2的腺病毒的外膜周围转移显著增加了高胆固醇血症兔带颈圈动脉的内膜增厚、巨噬细胞积聚、内皮血管细胞黏附分子-1表达和外膜新生血管形成，并增加了正常饮食喂养的兔的内膜与中膜比值。新生内膜巨噬细胞与PlGF受体Flt-1的表达增加有关。与apoE缺陷小鼠相比，apoE和PlGF均缺乏的小鼠早期动脉粥样硬化病变的大小和巨噬细胞含量降低。
局部腺病毒递送PlGF2促进高胆固醇血症兔动脉粥样硬化新生内膜形成，并且PlGF是apoE(-/-)小鼠早期动脉粥样硬化病变中巨噬细胞浸润所必需的。这些发现支持PlGF在动脉粥样硬化疾病发病机制中的新作用。
