Inhibition of apelin expression switches endothelial cells from proliferative to mature state in pathological retinal angiogenesis.
Inhibition of apelin expression switches endothelial cells from proliferative to mature state in pathological retinal angiogenesis.
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DOI：
10.1007/s10456-013-9349-6
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发表时间：
2013-07
期刊：
影响因子：
9.8
通讯作者：
Maeda, Sadaaki
中科院分区：
文献类型：
--
作者：
Kasai, Atsushi;Ishimaru, Yuki;Higashino, Kosuke;Kobayashi, Kohei;Yamamuro, Akiko;Yoshioka, Yasuhiro;Maeda, Sadaaki
壁细胞如周细胞向具有内皮管腔的开放血管的募集是血管成熟和预防病理性血管生成中出血的关键因素。到目前为止，我们对细胞从生长到成熟阶段转变的具体触发因素的理解仍然不完整。由于内皮细胞的快速生长导致周细胞的损失，我们假设，抑制内皮生长因子将促进周细胞的招聘，除了抑制病理性血管生成。在这里，我们证明，靶向敲低爱帕琳在内皮细胞中使用siRNA诱导单核细胞趋化蛋白-1（MCP-1）的表达，通过激活Smad 3，通过抑制PI 3 K/Akt途径。经apelin siRNA处理的内皮细胞条件培养液通过MCP-1及其受体途径促进血管平滑肌细胞迁移。此外，体内递送靶向爱帕琳的siRNA（其通过其受体APJ引起旺盛的内皮细胞增殖和病理性血管生成）导致氧诱导的视网膜病变模型中周细胞覆盖增加并抑制病理性血管生成。这些数据表明，爱帕琳不仅是一种有效的内皮生长因子，而且还限制周细胞募集，在内皮细胞增殖信号传导和壁募集的触发之间建立了新的联系。本文的在线版本（doi：10.1007/s10456-013-9349-6）包含补充材料，可供授权用户使用。
The recruitment of mural cells such as pericytes to patent vessels with an endothelial lumen is a key factor for the maturation of blood vessels and the prevention of hemorrhage in pathological angiogenesis. To date, our understanding of the specific trigger underlying the transition from cell growth to the maturation phase remains incomplete. Since rapid endothelial cell growth causes pericyte loss, we hypothesized that suppression of endothelial growth factors would both promote pericyte recruitment, in addition to inhibiting pathological angiogenesis. Here, we demonstrate that targeted knockdown of apelin in endothelial cells using siRNA induced the expression of monocyte chemoattractant protein-1 (MCP-1) through activation of Smad3, via suppression of the PI3K/Akt pathway. The conditioned medium of endothelial cells treated with apelin siRNA enhanced the migration of vascular smooth muscle cells, through MCP-1 and its receptor pathway. Moreover, in vivo delivery of siRNA targeting apelin, which causes exuberant endothelial cell proliferation and pathological angiogenesis through its receptor APJ, led to increased pericyte coverage and suppressed pathological angiogenesis in an oxygen-induced retinopathy model. These data demonstrate that apelin is not only a potent endothelial growth factor, but also restricts pericyte recruitment, establishing a new connection between endothelial cell proliferation signaling and a trigger of mural recruitment. The online version of this article (doi:10.1007/s10456-013-9349-6) contains supplementary material, which is available to authorized users.
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影响因子：
2.8
作者：
Abu El-Asrar, Ahmed M.;Struyf, Sofie;Van Damme, Jo
通讯作者：
Van Damme, Jo
缺乏周细胞会导致内皮增生和异常血管形态发生。
影响因子：
7.8
作者：
Hellstrom, M;Gerhardt, H;Kalen, M;Li, X;Eriksson, U;Wolburg, H;Betsholtz, C
通讯作者：
Betsholtz, C
影响因子：
4.8
作者：
Masri, B;Morin, N;Audigier, Y
通讯作者：
Audigier, Y
影响因子：
46.9
作者：
Agrawal, S;Kandimalla, ER
通讯作者：
Kandimalla, ER
影响因子：
4.4
作者：
Davies, Michael H.;Stempel, Andrew J.;Powers, Michael R.
通讯作者：
Powers, Michael R.