期刊
FASEB JOURNAL
卷 22, 期 5, 页码 1530-1539出版社
FEDERATION AMER SOC EXP BIOL
DOI: 10.1096/fj.07-9617com
关键词
angiogenesis; sprouting; basement membrane; VEGF
资金
- Biotechnology and Biological Sciences Research Council [BB/D014638/1] Funding Source: Medline
- Medical Research Council [G0300296] Funding Source: Medline
- BBSRC [BB/D014638/1] Funding Source: UKRI
- MRC [G0300296] Funding Source: UKRI
- Biotechnology and Biological Sciences Research Council [BB/D014638/1] Funding Source: researchfish
- Medical Research Council [G0300296] Funding Source: researchfish
Basement membranes (BMs) consisting of laminins, collagens, and heparan sulfate proteoglycans (HSPGs) are vital for proper endothelial cell function, but many aspects of their role in vascular development remain unknown. Here, we demonstrate that vascular structures within differentiating embryoid bodies are wrapped in a BM composed of alpha 4- and alpha 5-chain laminins, fibronectin, collagen IV, and HSPGs. In sprouting angiogenesis, laminins were produced by stalk cells, as well as the leading tip cell, and deposited along the sprout length, including tip cell filopodia. In embryonic stem cells deficient in laminins, due to lamc1 (laminin gamma 1) deletion, vascular development and organization were largely unaffected. However, the frequency of vessels with wide lumens was increased 4-fold. Laminin-deficient vessels were moreover characterized by increased fibronectin levels and enhanced endothelial cell proliferation. We conclude that laminins are dispensable for vascular development but that they regulate lumen formation in the absence of flow and vascular tone.
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