VEGF-C regulates lymphangiogenesis and capillary stability by regulation of PDGF-B
VEGF-C regulates lymphangiogenesis and capillary stability by regulation of PDGF-B
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DOI：
10.1152/ajpheart.00015.2009
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发表时间：
2009-11-01
影响因子：
4.8
通讯作者：
Sueishi, Katsuo
中科院分区：
文献类型：
--
作者：
Onimaru, Mitsuho;Yonemitsu, Yoshikazu;Sueishi, Katsuo
[10] Onimaru M，Yonemitsu Y，Fujii T，Tanii M，中野T，Nakagawa K，Kohno R，Hasegawa M，Nishikawa S，Sueishi K. VEGF-C通过调节PDGF-B调节淋巴管生成和毛细血管稳定性。Am J Physiol Heart Circ Physiol 297：H1685-H1696，2009.首次发表于2009年9月4日; doi：10.1152/ajpheart.00015.2009。新出现的证据表明，使用血小板衍生生长因子（PDGF）-BB的血管内皮细胞和壁细胞之间的紧密通信是至关重要的毛细血管生成过程中的稳定。然而，关于决定PDGF-BB表达的相关调节因子知之甚少。使用治疗性新生血管形成的小鼠模型，我们在这里表明，一个典型的淋巴管生成因子，血管内皮生长因子（VEGF）-C，是一个必不可少的调节器确定PDGF-BB表达血管稳定通过旁分泌的行动模式。使用中和抗体AFL-4阻断VEGF 3型受体（VEGFR 3）可阻断FGF-2介导的严重缺血后肢的保肢和血流恢复。有趣的是，抑制VEGFR 3活性不仅减少淋巴管生成，而且诱导毛细血管显著扩张，显示壁细胞解离。在这些小鼠中，VEGF-C和PDGF-B在诱导缺血后的后期上调，在第7天，当外源性FGF-2表达已经下降时，VEGFR 3或PDGF-BB活性的阻断分别降低了PDGF-B或VEGF-C的表达。这些结果清楚地表明，VEGF-C是一个关键的调解人，不仅为淋巴管生成，而且为毛细血管的稳定，必要的分子机制之间的通信内皮细胞和壁细胞在新血管形成。
Onimaru M, Yonemitsu Y, Fujii T, Tanii M, Nakano T, Nakagawa K, Kohno R, Hasegawa M, Nishikawa S, Sueishi K. VEGF-C regulates lymphangiogenesis and capillary stability by regulation of PDGF-B. Am J Physiol Heart Circ Physiol 297: H1685-H1696, 2009. First published September 4, 2009; doi:10.1152/ajpheart.00015.2009.-Emerging evidence indicates that the tight communication between vascular endothelial cells and mural cells using platelet-derived growth factor (PDGF)-BB is essential for capillary stabilization during the angiogenic process. However, little is known about the related regulator that determines PDGF-BB expression. Using murine models of therapeutic neovascularization, we here show that a typical lymphangiogenic factor, vascular endothelial growth factor (VEGF)-C, is an essential regulator determining PDGF-BB expression for vascular stabilization via a paracrine mode of action. The blockade of VEGF type 3 receptor (VEGFR3) using neutralizing antibody AFL-4 abrogated FGF-2-mediated limb salvage and blood flow recovery in severely ischemic hindlimb. Interestingly, inhibition of VEGFR3 activity not only diminished lymphangiogenesis, but induced marked dilatation of capillary vessels, showing mural cell dissociation. In these mice, VEGF-C and PDGF-B were upregulated in the later phase after induced ischemia, on day 7, when exogenous FGF-2 expression had already declined, and blockade of VEGFR3 or PDGF-BB activities diminished PDGF-B or VEGF-C expression, respectively. These results clearly indicate that VEGF-C is a critical mediator, not only for lymphangiogenesis, but also for capillary stabilization, the essential molecular mechanism of communication between endothelial cells and mural cells during neovascularization.