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Angiogenesis and Vascular Remodeling in Inflammation and Cancer: Biology and Architecture of the Vasculature

  • Chapter
Angiogenesis

Blood vessels proliferate by sprouting from existing vessels (angiogenesis) and undergo changes in phenotype (vascular remodeling) in inflammatory diseases, tumors, and many other chronic conditions. Changes in newly formed and remodeled blood vessels are disease-specific, as they reflect vascular adaptations to environmental cues unique to each condition. In inflamed tissues, vascular remodeling expands the vasculature and increases blood flow, plasma leakage, and inflammatory cell influx, which contribute to the pathophysiology and clinical manifestations of the disease. Remodeling of endothelial cells into a venular phenotype, typical of sustained inflammation, is accompanied by expression of molecules that promote endothelial gap formation and leukocyte rolling, attachment, and migration. Blood vessels in tumors differ from those in inflammation. Endothelial cells in tumors undergo disorganized sprouting, proliferation and regression, and become dependent on vascular endothelial growth factor (VEGF) or other factors for survival. The growing vasculature enables tumor enlargement, but structural defects impair endothelial barrier function and increase interstitial pressure and luminal resistance, diminish blood flow, and alter immune cell traffic. Oxygen delivery may be inadequate for tumor cell viability despite the rich vascularity. Inhibition of VEGF signaling in tumors stops sprouting angiogenesis and triggers regression of some tumor vessels while normalizing others. Some capillaries in normal thyroid, pancreatic islets, and intestine may also regress after VEGF blockade, but most remodeled vessels at sites of inflammation do not. Pericytes and empty sleeves of vascular basement membrane persist after endothelial cells regress and provide a scaffold for blood vessel regrowth, which can occur within days after the inhibition ends. The clinical efficacy of VEGF signaling inhibitors in cancer and age-related macular degeneration provides proof of concept and stimulates the search for even more effective agents. Further advances in vascular biology will lead to more powerful strategies for controlling blood vessel growth and regression in health and disease.

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Authors and Affiliations

  1. Department of Anatomy, University of California, San Francisco, CA, USA

    Donald M. McDonald

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  1. Donald M. McDonald
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Editors and Affiliations

  1. Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA

    William D. Figg

  2. Department of Surgery Harvard Medical School and Vascular Biology Program, Children's Hospital Boston, Boston, MA, USA

    Judah Folkman

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McDonald, D.M. (2008). Angiogenesis and Vascular Remodeling in Inflammation and Cancer: Biology and Architecture of the Vasculature. In: Figg, W.D., Folkman, J. (eds) Angiogenesis. Springer, Boston, MA. https://doi.org/10.1007/978-0-387-71518-6_2

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  • DOI: https://doi.org/10.1007/978-0-387-71518-6_2

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-0-387-71517-9

  • Online ISBN: 978-0-387-71518-6

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