Ohtani Kisho, Egashira Kensuke, Hiasa Ken-ichi, Zhao Qingwei, Kitamoto Shiro, Ishibashi Minako, Usui Makoto, Inoue Shujiro, Yonemitsu Yoshikazu, Sueishi Katsuo, Sata Masataka, Shibuya Masabumi, Sunagawa Kenji
Department of Cardiovascular Medicine, Graduate School of Medical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Circulation. 2004 Oct 19;110(16):2444-52. doi: 10.1161/01.CIR.0000145123.85083.66. Epub 2004 Oct 11.
Therapeutic angiogenesis by delivery of vascular endothelial growth factor (VEGF) has attracted attention. However, the role and function of VEGF in experimental restenosis (neointimal formation) after vascular intraluminal injury have not been addressed.
We report herein that blockade of VEGF by soluble VEGF receptor 1 (sFlt-1) gene transfer attenuated neointimal formation after intraluminal injury in rabbits, rats, and mice. sFlt-1 gene transfer markedly attenuated the early vascular inflammation and proliferation and later neointimal formation. sFlt-1 gene transfer also inhibited increased expression of inflammatory factors such as monocyte chemoattractant protein-1 and VEGF. Intravascular VEGF gene transfer enhanced angiogenesis in the adventitia but did not reduce neointimal formation.
Increased expression and activity of VEGF are essential in the development of experimental restenosis after intraluminal injury by recruiting monocyte-lineage cells.
通过递送血管内皮生长因子（VEGF）进行治疗性血管生成已引起关注。然而，VEGF在血管腔内损伤后实验性再狭窄（新生内膜形成）中的作用和功能尚未得到研究。
我们在此报告，通过可溶性VEGF受体1（sFlt-1）基因转移阻断VEGF可减轻兔、大鼠和小鼠腔内损伤后的新生内膜形成。sFlt-1基因转移显著减轻了早期血管炎症和增殖以及后期的新生内膜形成。sFlt-1基因转移还抑制了炎症因子如单核细胞趋化蛋白-1和VEGF表达的增加。血管内VEGF基因转移增强了外膜中的血管生成，但并未减少新生内膜形成。
VEGF表达和活性的增加通过募集单核细胞系细胞在腔内损伤后实验性再狭窄的发展中起关键作用。
