Wang Hang, Yin Yang-Guang, Huang Hao, Zhao Xiao-Hui, Yu Jie, Wang Qiang, Li Wei, Cai Ke-Yin, Ding Shi-Fang
Cadre Ward Two, Wuhan General Hospital of Guangzhou Military Command, Wuhan, 430070, China.
Intensive Care Unit, The sixth people's hospital of Chongqing, Nan'an District, Chongqing, 400060, China.
BMC Cardiovasc Disord. 2016 Sep 13;16(1):179. doi: 10.1186/s12872-016-0353-9.
Endothelial progenitor cells (EPCs) play important roles in the regeneration of the vascular endothelial cells (ECs). Platelet-derived growth factor receptor (PDGFR)-β is known to contribute to proliferation, migration, and angiogenesis of EPCs, this study aims to investigate effects of transplantation of EPCs overexpressing PDGFR-β on vascular regeneration.
We transplanted genetically modified EPCs overexpressing PDGFR-β into a mouse model with carotid artery injury. After 3 days of EPCs transplantation, the enhanced green fluorescent protein (EGFP)-expressing cells were found at the injury site and the lining of the lumen by laser scanning confocal microscope (LSCM). At 4, 7, and 14 days of the carotid artery injury, reendothelialization was evaluated by Evans Blue staining. Neointima formation was evaluated at day 14 with hematoxylin and eosin (HE) staining by calculating the neointimal area, medial area, and neointimal/media (NI/M) ratio. Intimal cell apoptosis was evaluated using TUNEL assay. Then we tested whether PDGF-BB-induced VSMC migration and PDGF-BB's function in reducing VSMC apoptosis can be attenuated by EPCs overexpressing PDGFR-β in a transwell co-culture system.
Our results showed that EPCs overexpressing PDGFR-β accelerates reendothelialization and mitigates neointimal formation at 14 days after injury. Moreover, we found that there is great possibility that EPCs overexpressing PDGFR-β enhanc VSMC apoptosis and suppress VSMC migration by competitive consumption of PDGF-BB in the early phase after carotid artery injury in mice.
We report the first in vivo and in vitro evidence that transplantation of genetically modified EPC can have a combined effect of both amplifying the reendothelialization capacity of EPCs and inhibiting neointima formation so as to facilitate better inhibition of adverse remodeling after vascular injury.
内皮祖细胞（EPCs）在血管内皮细胞（ECs）再生中发挥重要作用。已知血小板衍生生长因子受体（PDGFR）-β有助于EPCs的增殖、迁移和血管生成，本研究旨在探讨过表达PDGFR-β的EPCs移植对血管再生的影响。
我们将过表达PDGFR-β的基因修饰EPCs移植到颈动脉损伤的小鼠模型中。EPCs移植3天后，通过激光扫描共聚焦显微镜（LSCM）在损伤部位和管腔内膜发现表达增强绿色荧光蛋白（EGFP）的细胞。在颈动脉损伤后的第4、7和14天，通过伊文思蓝染色评估再内皮化。在第14天用苏木精和伊红（HE）染色，通过计算新生内膜面积、中膜面积和新生内膜/中膜（NI/M）比值评估新生内膜形成。使用TUNEL法评估内膜细胞凋亡。然后我们在transwell共培养系统中测试过表达PDGFR-β的EPCs是否能减弱血小板源性生长因子BB（PDGF-BB）诱导的血管平滑肌细胞（VSMC）迁移以及PDGF-BB在减少VSMC凋亡中的作用。
我们的结果表明，过表达PDGFR-β的EPCs在损伤后14天加速再内皮化并减轻新生内膜形成。此外，我们发现过表达PDGFR-β的EPCs很有可能通过在小鼠颈动脉损伤后的早期竞争性消耗PDGF-BB来增强VSMC凋亡并抑制VSMC迁移。
我们首次报告了体内和体外证据，即基因修饰的EPCs移植可具有放大EPCs的再内皮化能力和抑制新生内膜形成的联合作用，从而有助于更好地抑制血管损伤后的不良重塑。
