Placental growth factor promotes atherosclerotic intimal thickening and macrophage accumulation
Placental growth factor promotes atherosclerotic intimal thickening and macrophage accumulation
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DOI：
10.1161/circulationaha.104.495887
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发表时间：
2005-05-31
期刊：
影响因子：
37.8
通讯作者：
Zachary, IC
中科院分区：
文献类型：
--
作者：
Khurana, R;Moons, L;Zachary, IC
背景-胎盘生长因子（PlGF）与慢性炎症性疾病的病理生理学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研究。我们研究了外源性PlGF（通过腺病毒基因转移）对颈动脉颈环诱导的动脉粥样硬化内膜增厚和巨噬细胞聚集的影响，并检测了PlGF缺乏对载脂蛋白E缺乏的兔颈动脉粥样硬化的影响。（apoE（-/-））小鼠。方法和结果-外膜周转移PlGF 2编码腺病毒显著增加内膜增厚，巨噬细胞积累，内皮血管细胞粘附分子-1的表达和高胆固醇血症兔颈动脉的外膜新生血管形成，并增加正常饮食兔的内膜-中膜比率。新生内膜巨噬细胞与PlGF受体Flt-1的表达增加相关。与apoE缺陷小鼠相比，apoE和PlGF缺陷小鼠的早期动脉粥样硬化病变的大小和巨噬细胞含量降低。结论-局部腺病毒PlGF 2递送促进高胆固醇血症兔中致动脉粥样硬化新生内膜形成，并且PlGF是apoE（-/-）小鼠中早期动脉粥样硬化病变中巨噬细胞浸润所需的。这些发现支持了一个新的作用，PlGF在动脉粥样硬化性疾病的发病机制。
Background - 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.Methods and Results - 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.Conclusions - 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.