Vesalius Research Center, VIB, KULeuven, Campus Gasthuisberg, Herestraat 49, Box 912, 3000 Leuven, Belgium.
Cardiovasc Res. 2010 Apr 1;86(1):29-36. doi: 10.1093/cvr/cvp380. Epub 2009 Dec 1.
Placental growth factor (PlGF), a homologue of vascular endothelial growth factor, is a pleiotropic cytokine with a pro-inflammatory activity. Previous gene-inactivation studies revealed that the loss of PlGF delays atherosclerotic lesion development and inhibits macrophage infiltration, but the activity of an anti-PlGF antibody (alphaPlGF mAb) has not been evaluated yet.
We characterized the potential of short-term delivery of alphaPlGF mAb in inhibiting lesion development in ApoE-deficient mice (apoE(-/-)) and in CD4:TGFbetaRII(DN) x apoE(-/-) mice, a more severe atherosclerosis model. Short-term treatment of alphaPlGF mAb reduces early atherosclerotic plaque size and inflammatory cell infiltration in the lesion.
These pharmacological alphaPlGF mAb results confirm previous genetic evidence that inhibition of PlGF slows down early atherosclerotic lesion development. Furthermore, the phenocopy of genetic and pharmacological loss-of-function strategies underscores that alphaPlGF acts by selectively neutralizing PlGF.
胎盘生长因子（PlGF）是血管内皮生长因子的同源物，是一种具有促炎活性的多功能细胞因子。先前的基因敲除研究表明，PlGF 的缺失会延迟动脉粥样硬化病变的发展并抑制巨噬细胞浸润，但尚未评估抗 PlGF 抗体（alphaPlGF mAb）的活性。
我们研究了短期给予 alphaPlGF mAb 抑制载脂蛋白 E 缺陷（apoE(-/-)）小鼠和 CD4:TGFbetaRII(DN) x apoE(-/-)小鼠（一种更严重的动脉粥样硬化模型）中病变发展的潜力。alphaPlGF mAb 的短期治疗可减小早期动脉粥样硬化斑块的大小并减少病变中的炎症细胞浸润。
这些药理学 alphaPlGF mAb 结果证实了先前的遗传证据，即抑制 PlGF 可减缓早期动脉粥样硬化病变的发展。此外，基因敲除和药理学失活策略的表型复制强调了 alphaPlGF 通过选择性中和 PlGF 起作用。
