Journal article
NO mediates mural cell recruitment and vessel morphogenesis in murine melanomas and tissue-engineered blood vessels
The Journal of clinical investigation, v 115(7), pp 1816-1827
09 Jun 2005
PMID: 15951843
Featured in Collection : UN Sustainable Development Goals @ Drexel
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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Details
- Title
- NO mediates mural cell recruitment and vessel morphogenesis in murine melanomas and tissue-engineered blood vessels
- Creators
- Satoshi Kashiwagi - Edwin L. Steele Laboratory, Department of Radiation Oncology, and Cardiovascular Research Center, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.Yotaro Izumi - Edwin L. Steele Laboratory, Department of Radiation Oncology, and Cardiovascular Research Center, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA. Departments of Physiology and Bioengineering, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USATakeshi Gohongi - Edwin L. Steele Laboratory, Department of Radiation Oncology, and Cardiovascular Research Center, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA. Departments of Physiology and Bioengineering, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USAZoe N. Demou - Edwin L. Steele Laboratory, Department of Radiation Oncology, and Cardiovascular Research Center, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA. Departments of Physiology and Bioengineering, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USALei Xu - Edwin L. Steele Laboratory, Department of Radiation Oncology, and Cardiovascular Research Center, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA. Departments of Physiology and Bioengineering, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USAPaul L. Huang - Edwin L. Steele Laboratory, Department of Radiation Oncology, and Cardiovascular Research Center, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA. Departments of Physiology and Bioengineering, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USADonald G. Buerk - University of PennsylvaniaLance L. Munn - Edwin L. Steele Laboratory, Department of Radiation Oncology, and Cardiovascular Research Center, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA. Departments of Physiology and Bioengineering, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USARakesh K. Jain - Edwin L. Steele Laboratory, Department of Radiation Oncology, and Cardiovascular Research Center, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA. Departments of Physiology and Bioengineering, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USADai Fukumura - Edwin L. Steele Laboratory, Department of Radiation Oncology, and Cardiovascular Research Center, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA. Departments of Physiology and Bioengineering, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA
- Publication Details
- The Journal of clinical investigation, v 115(7), pp 1816-1827
- Publisher
- American Society for Clinical Investigation
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- School of Biomedical Engineering, Science, and Health Systems
- Web of Science ID
- WOS:000230292800021
- Scopus ID
- 2-s2.0-22144456034
- Other Identifier
- 991019231726004721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Medicine, Research & Experimental