Vascular permeability factor/vascular endothelial growth factor induces lymphangiogenesis as well as angiogenesis.
Vascular permeability factor/vascular endothelial growth factor induces lymphangiogenesis as well as angiogenesis.
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DOI：
10.1084/jem.20021244
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发表时间：
2002-12-02
期刊：
影响因子：
--
通讯作者：
Dvorak HF
中科院分区：
文献类型：
--
作者：
Nagy JA;Vasile E;Feng D;Sundberg C;Brown LF;Detmar MJ;Lawitts JA;Benjamin L;Tan X;Manseau EJ;Dvorak AM;Dvorak HF
血管通透性因子/血管内皮生长因子（VPF/VEGF，VEGF-A）是一种多功能细胞因子，在病理性血管生成中起重要作用。使用腺病毒载体工程表达鼠VEGF-A164，我们以前研究的步骤和机制，这种细胞因子诱导成年免疫缺陷小鼠形成新的血管，并证明，新形成的血管非常相似，发现在VEGF-A表达肿瘤。我们现在报道，除了诱导血管生成，VEGF-A164还诱导强烈的淋巴管生成反应。这一发现是意料之外的，因为淋巴管生成被认为是由VPF/VEGF家族的其他成员，即VEGF-C和VEGF-D介导的。由VEGF-A164产生的新的“巨大”淋巴结在结构和功能上都异常：大大增大，瓣膜功能不全，血流缓慢，淋巴清除延迟。它们非常类似于淋巴管瘤/淋巴管畸形中发现的大淋巴管，可能暗示VEGF-A在这些病变的发病机制中。然而，血管生成反应仅维持只要VEGF-A表达，巨大的神经胶质细胞，一旦形成，成为VEGF-A的独立性和无限期地持续，长时间后VEGF-A表达停止。这些发现提高了在VEGF-A过表达的其他病理中发生类似的异常炎症的可能性，例如，恶性肿瘤和慢性炎症。
Vascular permeability factor/vascular endothelial growth factor (VPF/VEGF, VEGF-A) is a multifunctional cytokine with important roles in pathological angiogenesis. Using an adenoviral vector engineered to express murine VEGF-A164, we previously investigated the steps and mechanisms by which this cytokine induced the formation of new blood vessels in adult immunodeficient mice and demonstrated that the newly formed blood vessels closely resembled those found in VEGF-A–expressing tumors. We now report that, in addition to inducing angiogenesis, VEGF-A164 also induces a strong lymphangiogenic response. This finding was unanticipated because lymphangiogenesis has been thought to be mediated by other members of the VPF/VEGF family, namely, VEGF-C and VEGF-D. The new “giant” lymphatics generated by VEGF-A164 were structurally and functionally abnormal: greatly enlarged with incompetent valves, sluggish flow, and delayed lymph clearance. They closely resembled the large lymphatics found in lymphangiomas/lymphatic malformations, perhaps implicating VEGF-A in the pathogenesis of these lesions. Whereas the angiogenic response was maintained only as long as VEGF-A was expressed, giant lymphatics, once formed, became VEGF-A independent and persisted indefinitely, long after VEGF-A expression ceased. These findings raise the possibility that similar, abnormal lymphatics develop in other pathologies in which VEGF-A is overexpressed, e.g., malignant tumors and chronic inflammation.
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DOI：
10.1073/pnas.95.24.14389
发表时间：
1998-11-24
影响因子：
11.1
作者：
Cao, YH;Linden, P;Alitalo, K
通讯作者：
Alitalo, K
DOI：
10.1073/pnas.95.2.548
发表时间：
1998-01-20
影响因子：
11.1
作者：
Achen, MG;Jeltsch, M;Stacker, SA
通讯作者：
Stacker, SA
影响因子：
2.7
作者：
Oh, SJ;Jeltsch, MM;Wilting, J
通讯作者：
Wilting, J
影响因子：
30.8
作者：
Karkkainen, MJ;Ferrell, RE;Finegold, DN
通讯作者：
Finegold, DN
影响因子：
5
作者：
Huang, HY;Ho, CC;Hsu, SM
通讯作者：
Hsu, SM