Fibroblast growth factor-2/platelet-derived growth factor enhances atherosclerotic plaque stability
Fibroblast growth factor-2/platelet-derived growth factor enhances atherosclerotic plaque stability
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成纤维细胞生长因子-2/血小板衍生生长因子增强动脉粥样硬化斑块稳定性
DOI：
10.1111/jcmm.14850
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发表时间：
2019-11-21
影响因子：
5.3
通讯作者：
Zhang，Yun
中科院分区：
文献类型：
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作者：
Mao，Yang;Liu，Xiao Qiong;Zhang，Yun
增加的未成熟新生血管有助于斑块生长和不稳定性。在这里，我们研究了一种建立功能和稳定的新血管网络以增加斑块稳定性的方法。将家兔进行主动脉球囊损伤，并分为6组：假手术组、载体组和慢病毒转染组，分别转染血管内皮生长因子-A（VEGF）-A、成纤维细胞生长因子（FGF）-2、血小板衍生生长因子（PDGF）-BB和FGF-2 + PDGF-BB。通过血管内超声引导将慢病毒经皮注射到腹主动脉的中膜外膜中，并评价注射部位的斑块破裂率、斑块易损性指数和斑块新生血管密度。共聚焦显微镜，普鲁士蓝，伊文思蓝，免疫荧光和透射电镜用于评估新生血管功能和周细胞覆盖。为了评估FGF-2/PDGF-BB对周细胞迁移的影响，我们使用间充质祖细胞系10 T1/2作为体外模型。VEGF-A-和FGF-2-过表达增加了未成熟新生血管的数量，导致斑块内出血和炎性细胞浸润，最终导致斑块脆弱性;然而，FGF-2/PDGF-BB通过增加新生血管周细胞覆盖率诱导成熟和功能性新生血管。此外，10 T1/2细胞的体外分析显示，FGF-2/PDGF-BB诱导depsin-2表达并增强VEGF受体-2降解，这与体内数据一致，对周细胞功能产生负调节。这些结果表明，FGF-2和PDGF-BB的组合促进了斑块新生血管的功能和成熟，从而代表了易损斑块的新的潜在治疗策略。
Increased immature neovessels contribute to plaque growth and instability. Here, we investigated a method to establish functional and stable neovessel networks to increase plaque stability. Rabbits underwent aortic balloon injury and were divided into six groups: sham, vector and lentiviral transfection with vascular endothelial growth factor‐A (VEGF)‐A, fibroblast growth factor (FGF)‐2, platelet‐derived growth factor (PDGF)‐BB and FGF‐2 + PDGF‐BB. Lentivirus was percutaneously injected into the media‐adventitia of the abdominal aorta by intravascular ultrasound guidance, and plaque‐rupture rate, plaque‐vulnerability index and plaque neovessel density at the injection site were evaluated. Confocal microscopy, Prussian Blue assay, Evans Blue, immunofluorescence and transmission electron microscopy were used to assess neovessel function and pericyte coverage. To evaluate the effect of FGF‐2/PDGF‐BB on pericyte migration, we used the mesenchymal progenitor cell line 10T1/2 as an in vitro model. VEGF‐A‐ and FGF‐2‐overexpression increased the number of immature neovessels, which caused intraplaque haemorrhage and inflammatory cell infiltration, eventually resulting in the plaque vulnerability; however, FGF‐2/PDGF‐BB induced mature and functional neovessels, through increased neovessel pericyte coverage. Additionally, in vitro analysis of 10T1/2 cells revealed that FGF‐2/PDGF‐BB inducedepsin‐2expression and enhanced the VEGF receptor‐2 degradation, which negatively regulated pericyte function consistent with the in vivo data. These results showed that the combination of FGF‐2 and PDGF‐BB promoted the function and maturation of plaque neovessels, thereby representing a novel potential treatment strategy for vulnerable plaques.