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NO mediates mural cell recruitment and vessel morphogenesis in murine melanomas and tissue-engineered blood vessels
Journal article   Open access   Peer reviewed

NO mediates mural cell recruitment and vessel morphogenesis in murine melanomas and tissue-engineered blood vessels

Satoshi Kashiwagi, Yotaro Izumi, Takeshi Gohongi, Zoe N. Demou, Lei Xu, Paul L. Huang, Donald G. Buerk, Lance L. Munn, Rakesh K. Jain and Dai Fukumura
The Journal of clinical investigation, v 115(7), pp 1816-1827
09 Jun 2005
PMID: 15951843
url
https://doi.org/10.1172/jci24015View
Published, Version of Record (VoR)Maybe Open Access (Publisher Bronze) Open
url
https://doi.org/10.1172/JCI24015View
Published, Version of Record (VoR) Open

Abstract

NO has been shown to mediate angiogenesis; however, its role in vessel morphogenesis and maturation is not known. Using intravital microscopy, histological analysis, α–smooth muscle actin and chondroitin sulfate proteoglycan 4 staining, microsensor NO measurements, and an NO synthase (NOS) inhibitor, we found that NO mediates mural cell coverage as well as vessel branching and longitudinal extension but not the circumferential growth of blood vessels in B16 murine melanomas. NO-sensitive fluorescent probe 4,5-diaminofluorescein imaging, NOS immunostaining, and the use of NOS-deficient mice revealed that eNOS in vascular endothelial cells is the predominant source of NO and induces these effects. To further dissect the role of NO in mural cell recruitment and vascular morphogenesis, we performed a series of independent analyses. Transwell and under-agarose migration assays demonstrated that endothelial cell–derived NO induces directional migration of mural cell precursors toward endothelial cells. An in vivo tissue-engineered blood vessel model revealed that NO mediates endothelial–mural cell interaction prior to vessel perfusion and also induces recruitment of mural cells to angiogenic vessels, vessel branching, and longitudinal extension and subsequent stabilization of the vessels. These data indicate that endothelial cell–derived NO induces mural cell recruitment as well as subsequent morphogenesis and stabilization of angiogenic vessels.

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Collaboration types
Domestic collaboration
Web of Science research areas
Medicine, Research & Experimental
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