Perlecan maintains microvessel integrity in vivo and modulates their formation in vitro.
Perlecan maintains microvessel integrity in vivo and modulates their formation in vitro.
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DOI：
10.1371/journal.pone.0053715
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Costell M
中科院分区：
文献类型：
--
作者：
Gustafsson E;Almonte-Becerril M;Bloch W;Costell M
串珠素是一种硫酸乙酰肝素蛋白聚糖，在血管发生过程中组装到血管基底膜（BM）中。在本研究中，我们研究了血管形成的小鼠，畸胎瘤和胚状体（EB）的情况下，串珠素。我们发现串珠素在胚胎第12.5天之前一直参与血管的形成和成熟。在发育的后期，40%的突变胚胎在大脑和皮肤中显示出扩张的微血管，这些微血管破裂并导致严重的眼睑炎。令人惊讶的是，来源于串珠素缺失ES细胞的畸胎瘤显示串珠素缺陷内皮细胞对明显正常的肿瘤血管系统的有效贡献。然而，在串珠蛋白聚糖缺陷的EB中，内皮网络所占据的面积和血管分支的数量显着减少。添加FGF-2而不是VEGF 165挽救了突变ES细胞的体外缺陷。此外，在EB基质中不存在串珠素的情况下，较低水平的FGF被结合、储存并可用于细胞表面呈递。总之，这些发现表明串珠素支持脑和皮肤内皮下BM的维持，并通过调节FGF-2功能促进血管和血管生成。
Perlecan is a heparan sulfate proteoglycan assembled into the vascular basement membranes (BMs) during vasculogenesis. In the present study we have investigated vessel formation in mice, teratomas and embryoid bodies (EBs) in the absence of perlecan. We found that perlecan was dispensable for blood vessel formation and maturation until embryonic day (E) 12.5. At later stages of development 40% of mutant embryos showed dilated microvessels in brain and skin, which ruptured and led to severe bleedings. Surprisingly, teratomas derived from perlecan-null ES cells showed efficient contribution of perlecan-deficient endothelial cells to an apparently normal tumor vasculature. However, in perlecan-deficient EBs the area occupied by an endothelial network and the number of vessel branches were significantly diminished. Addition of FGF-2 but not VEGF165 rescued the in vitro deficiency of the mutant ES cells. Furthermore, in the absence of perlecan in the EB matrix lower levels of FGFs are bound, stored and available for cell surface presentation. Altogether these findings suggest that perlecan supports the maintenance of brain and skin subendothelial BMs and promotes vasculo- and angiogenesis by modulating FGF-2 function.
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影响因子：
4.8
作者：
Goyal, Atul;Pal, Nutan;Iozzo, Renato V.
通讯作者：
Iozzo, Renato V.
影响因子：
9.8
作者：
Arikawa-Hirasawa, E;Le, AH;Yamada, Y
通讯作者：
Yamada, Y
影响因子：
20.1
作者：
Costell, M;Carmona, R;Muñoz-Chápuli, R
通讯作者：
Muñoz-Chápuli, R
影响因子：
--
作者：
Giros, Amparo;Morante, Javier;Costell, Mercedes
通讯作者：
Costell, Mercedes
DOI：
10.1161/01.atv.0000063109.94810.ee
发表时间：
2003-04-01
影响因子：
8.7
作者：
Kinsella, MG;Tran, PK;Wight, TN
通讯作者：
Wight, TN