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Esophageal and Gastrointestinal Microcirculation: Essential for Mucosal Protection, a Target for Injury, and a Critical Component of Injury and Ulcer Healing

  • Conference paper
Organ Microcirculation

Part of the book series: Keio University International Symposia for Life Sciences and Medicine ((KEIO,volume 13))

Summary

Blood flow through the network of mucosal microvessels in the gastrointestinal tract is essential for delivery of oxygen and nutrients to all mucosal constituents. The endothelial cells lining the microvessels, although protected by prostaglandins, are major targets for injury by various noxious factors, such as ethanol, nonsteroidal anti-inflammatory drugs (NSAIDs), ischemia-reperfusion, and free radicals. Endothelial injury results in formation of thrombi, microvascular stasis, and hypoxia, leading to tissue necrosis in the form of erosions or ulcers. Quantitative histologic, Transmission (TEM) and scanning electron microscopy (SEM) studies show that acute mucosal injury such as erosion triggers angiogenesis in the mucosal microvessels bordering necrosis: endothelial sprouting, formation of endothelial tubes ultimately leading to restoration of microvessels in regenerating tissue. The major molecular trigger for the initiation of angiogenesis in injured esophageal and gastric mucosa is accumulation of hypoxia inducible factor-1α (HIF-1α), which activates the genes encoding vascular endothelial growth factor (VEGF), its receptor, and angiopoietins that regulate angiogenesis. During healing of esophageal or gastric ulcers, granulation tissue, consisting of fibroblasts and proliferating endothelial cells forming microvessels, develops at the ulcer base. The newly formed microvessels, supported by fibroblasts and smooth muscle cells, sprout into the ulcerated area and restore the microvasculature in the ulcer scar. The molecular mechanisms stimulating angiogenesis in granulation tissue include activation of HIF-1α, egr-1, and genes encoding basic fibroblast growth factor, VEGF, angiopoietin-1, angiopoietin- 2, their receptors, and cyclooxygenase-2. The latter co-localizes with upregulated VEGF in esophageal and gastric ulcers. The scars of healed ulcers demonstrate prominent microvascular abnormalities detected by cast/SEM and vascular permeability studies. NSAIDs inhibit angiogenesis by interfering with MAP/Erk2 kinase, actin cytoskeleton, and D1 cyclin. Such actions are likely responsible for NSAID interference with ulcer healing. Our studies demonstrated that gene therapy with a single local injection of VEGF and angiopoietin-1 cDNAs stimulates angiogenesis, promotes restoration of microvascular network, and accelerates healing of experimental gastric and esophageal ulcers.

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Authors and Affiliations

  1. Department of Gastroenterology, VA Medical Center, Long Beach and the University of California, Irvine, 5901 East 7th Street, Long Beach, CA, 90822-5201, USA

    Andrzej S. Tarnawski, Jianyuan Chai & Michael K. Jones

Authors
  1. Andrzej S. Tarnawski
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  2. Jianyuan Chai
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  3. Michael K. Jones
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Editor information

Editors and Affiliations

  1. Department of Internal Medicine School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan

    Hiromasa Ishii M.D., Ph.D. (Professor Emeritus) & Hidekazu Suzuki M.D., Ph.D. (Assistant Professor) (Professor Emeritus) &  (Assistant Professor)

  2. Department of Biochemistry and Integrated Medical Biology School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan

    Makoto Suematsu M.D., Ph.D. (Professor) (Professor)

  3. Department of System Design Engineering Faculty of Science and Technology, Keio University, 3-14-1 Hiyoshi, Kohoku-ku, Yokohama, Kanagawa, 223-8522, Japan

    Kazuo Tanishita Ph.D. (Professor) (Professor)

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© 2005 Springer-Verlag Tokyo

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Tarnawski, A.S., Chai, J., Jones, M.K. (2005). Esophageal and Gastrointestinal Microcirculation: Essential for Mucosal Protection, a Target for Injury, and a Critical Component of Injury and Ulcer Healing. In: Ishii, H., Suematsu, M., Tanishita, K., Suzuki, H. (eds) Organ Microcirculation. Keio University International Symposia for Life Sciences and Medicine, vol 13. Springer, Tokyo. https://doi.org/10.1007/4-431-27174-0_7

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  • DOI: https://doi.org/10.1007/4-431-27174-0_7

  • Publisher Name: Springer, Tokyo

  • Print ISBN: 978-4-431-22135-7

  • Online ISBN: 978-4-431-27174-1

  • eBook Packages: MedicineMedicine (R0)

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