Regulated angiogenesis and vascular regression in mice overexpressing vascular endothelial growth factor in airways
Regulated angiogenesis and vascular regression in mice overexpressing vascular endothelial growth factor in airways
复制标题
DOI：
10.1016/s0002-9440(10)63369-x
复制
发表时间：
2004-10-01
影响因子：
6
通讯作者：
McDonald, DM
中科院分区：
文献类型：
--
作者：
Baluk, P;Lee, CG;McDonald, DM
血管生成和血管重塑发生在包括哮喘在内的许多炎症性疾病中。在这项研究中，我们确定了在CC10启动子驱动的气道上皮细胞中，血管内皮生长因子(VEGF)诱导的转基因系统中血管生成和血管重塑的时程和可逆性。开启血管内皮生长因子表达后1天，内皮芽从小静脉向上皮细胞生长，3~5天内皮细胞大量生长。血管密度在7天时达到基线的两倍。许多新生血管明显大于正常，有开窗孔，并穿透上皮。尽管周细胞被和基底膜提示新生血管在7d就已经成熟，但当血管内皮生长因子被切断时，新生血管在3d内开始消退，表现为淤滞和管腔闭塞，炎性细胞涌入，内皮细胞和周细胞回缩和凋亡。血管密度在停用VEGF后28天内恢复正常。我们的研究揭示了呼吸道血管生成和消退的动态本质。血管在几天内可通过萌发血管生成而对血管产生反应，但在血管内皮生长停止后血管退缩较慢，并以空的基底膜袖子的形式留下以前的程度的历史记录。
Angiogenesis and vascular remodeling occurs in many inflammatory diseases, including asthma. in this study, we determined the time course and reversibility of the angiogenesis and vascular remodeling produced by vascular endothelial growth factor (VEGF) in a tet-on inducible transgenic system driven by the CC10 promoter in airway epithelium. One day after switching on VEGF expression, endothelial sprouts arose from venules, grew toward the epithelium, and were abundant by 3 to 5 days. Vessel density reached twice baseline by 7 days. many new vessels were significantly larger than normal, were fenestrated, and penetrated the epithelium. Despite their mature appearance at 7 days suggested by their pericyte coat and basement membrane, the new vessels started to regress within 3 days when VEGF was switched off, showing stasis and luminal occlusion, influx of inflammatory cells, and retraction and apoptosis of endothelial cells and pericytes. Vessel density returned to normal within 28 days after VEGF withdrawal. Our study showed the dynamic nature of airway angiogenesis and regression. Blood vessels can respond to VEGF by sprouting angiogenesis within a few days, but regress more slowly after VEGF withdrawal, and leave a historical record of their previous extent in the form of empty basement membrane sleeves.