Abstract
This paper reviews and updates current views on gastric mucosal injury with a focus on the microvascular endothelium as the key target and the role of the anti-apoptosis protein survivin. Under normal conditions, mucosal integrity is maintained by well structured and mutually amplifying defense mechanisms, which include pre-epithelial “barrier” - the first line of defense; and, an epithelial “barrier”. Other important defense mechanisms of gastric mucosa include: continuous epithelial cell renewal, blood flow through mucosal microvessels (providing oxygen and nutrients), an endothelial microvascular “barrier,” sensory innervation, and generation of PGs, nitric oxide and hydrogen sulfide. The microvascular endothelium lining gastric mucosal blood microvessels severs not only as a barrier but is a biologically active tissue involved in many synthetic and metabolic functions. It allows transport of oxygen and nutrients, and produces prostaglandins and leukotriens, procoagulant factors, nitric oxide, endothelin, ghrelin, HSP, growth factors such VEGF, bFGF, angiopoietin 2 and others, specific types of collagen, plasminogen activator, and can also actively contract. Accumulating evidence indicates that the gastric microvascular endothelium is a critical target for injury by ethanol, NSAIDs, free radicals, ischemiareperfusion and other damaging factors. The injury - microvessel rupture, plasma and erythrocyte extravasation, platelet aggregation and fibrin deposition caused by these damaging factors - occurs early (1-5 min), precedes glandular epithelial cell injury and results in cessation of blood flow, ischemia, hypoxia and impaired oxygen and nutrient transport. As a consequence, mucosal necrosis develops. One of the main reasons for the increased susceptibility of gastric microvascular endothelial (vs. epithelial) cells to injury is reduced expression levels of survivin, an anti-apoptosis protein, which is a regulator of both proliferation and cell survival.
Keywords: Gastric mucosa, injury, microvessels, endothelium, survivin, apoptosis, anti-apoptosis, pre-epithelial “barrier”, endothelial microvascular, biologically active tissue, proliferation and cell survival
Current Medicinal Chemistry
Title: The Mechanisms of Gastric Mucosal Injury: Focus on Microvascular Endothelium as a Key Target
Volume: 19 Issue: 1
Author(s): A. S. Tarnawski, A. Ahluwalia and M. K. Jones
Affiliation:
Keywords: Gastric mucosa, injury, microvessels, endothelium, survivin, apoptosis, anti-apoptosis, pre-epithelial “barrier”, endothelial microvascular, biologically active tissue, proliferation and cell survival
Abstract: This paper reviews and updates current views on gastric mucosal injury with a focus on the microvascular endothelium as the key target and the role of the anti-apoptosis protein survivin. Under normal conditions, mucosal integrity is maintained by well structured and mutually amplifying defense mechanisms, which include pre-epithelial “barrier” - the first line of defense; and, an epithelial “barrier”. Other important defense mechanisms of gastric mucosa include: continuous epithelial cell renewal, blood flow through mucosal microvessels (providing oxygen and nutrients), an endothelial microvascular “barrier,” sensory innervation, and generation of PGs, nitric oxide and hydrogen sulfide. The microvascular endothelium lining gastric mucosal blood microvessels severs not only as a barrier but is a biologically active tissue involved in many synthetic and metabolic functions. It allows transport of oxygen and nutrients, and produces prostaglandins and leukotriens, procoagulant factors, nitric oxide, endothelin, ghrelin, HSP, growth factors such VEGF, bFGF, angiopoietin 2 and others, specific types of collagen, plasminogen activator, and can also actively contract. Accumulating evidence indicates that the gastric microvascular endothelium is a critical target for injury by ethanol, NSAIDs, free radicals, ischemiareperfusion and other damaging factors. The injury - microvessel rupture, plasma and erythrocyte extravasation, platelet aggregation and fibrin deposition caused by these damaging factors - occurs early (1-5 min), precedes glandular epithelial cell injury and results in cessation of blood flow, ischemia, hypoxia and impaired oxygen and nutrient transport. As a consequence, mucosal necrosis develops. One of the main reasons for the increased susceptibility of gastric microvascular endothelial (vs. epithelial) cells to injury is reduced expression levels of survivin, an anti-apoptosis protein, which is a regulator of both proliferation and cell survival.
Export Options
About this article
Cite this article as:
S. Tarnawski A., Ahluwalia A. and K. Jones M., The Mechanisms of Gastric Mucosal Injury: Focus on Microvascular Endothelium as a Key Target, Current Medicinal Chemistry 2012; 19 (1) . https://dx.doi.org/10.2174/092986712803414079
DOI https://dx.doi.org/10.2174/092986712803414079 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
Call for Papers in Thematic Issues
Advances in Medicinal Chemistry: From Cancer to Chronic Diseases.
The broad spectrum of the issue will provide a comprehensive overview of emerging trends, novel therapeutic interventions, and translational insights that impact modern medicine. The primary focus will be diseases of global concern, including cancer, chronic pain, metabolic disorders, and autoimmune conditions, providing a broad overview of the advancements in ...read more
Approaches to the treatment of chronic inflammation
Chronic inflammation is a hallmark of numerous diseases, significantly impacting global health. Although chronic inflammation is a hot topic, not much has been written about approaches to its treatment. This thematic issue aims to showcase the latest advancements in chronic inflammation treatment and foster discussion on future directions in this ...read more
Cellular and Molecular Mechanisms of Non-Infectious Inflammatory Diseases: Focus on Clinical Implications
The Special Issue covers the results of the studies on cellular and molecular mechanisms of non-infectious inflammatory diseases, in particular, autoimmune rheumatic diseases, atherosclerotic cardiovascular disease and other age-related disorders such as type II diabetes, cancer, neurodegenerative disorders, etc. Review and research articles as well as methodology papers that summarize ...read more
Chalcogen-modified nucleic acid analogues
Chalcogen-modified nucleosides, nucleotides and oligonucleotides have been of great interest to scientific research for many years. The replacement of oxygen in the nucleobase, sugar or phosphate backbone by chalcogen atoms (sulfur, selenium, tellurium) gives these biomolecules unique properties resulting from their altered physical and chemical properties. The continuing interest in ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Galectin-9 in Cancer Therapy
Recent Patents on Endocrine, Metabolic & Immune Drug Discovery Nanocarriers for the Simultaneous Co-Delivery of Therapeutic Genes and Anticancer Drugs
Current Pharmaceutical Biotechnology Pharmacological Interference With Protein-protein Interactions of Akinase Anchoring Proteins as a Strategy for the Treatment of Disease
Current Drug Targets Between Bench and Bed Side: PI3K Inhibitors
Current Molecular Pharmacology Application of Charge Transfer Reactions for the Quantitative Spectrophotometric Determination of Cyclophosphamide in Pure and Pharmaceutical Formulation
Current Pharmaceutical Analysis Drosophila melanogaster in the Study of Human Neurodegeneration
CNS & Neurological Disorders - Drug Targets The Prolyl-Aminodipeptidases and their Inhibitors as Therapeutic Targets for Fibrogenic Disorders
Mini-Reviews in Medicinal Chemistry DNA Repair in Premature Aging Disorders and Neurodegeneration
Current Aging Science Targeted Theranostics Against Solid Cancer Using Metal Bond Milk Protein and Aptamers
Current Topics in Medicinal Chemistry The Role of Cytochrome P450 in Cytotoxic Bioactivation: Future Therapeutic Directions
Current Cancer Drug Targets A Role for the Inflammatory Mediators Cox-2 and Metalloproteinases in Cancer Stemness
Anti-Cancer Agents in Medicinal Chemistry HtrA Serine Proteases as Potential Therapeutic Targets in Cancer
Current Cancer Drug Targets Characterizing the Relationship Between the Chemical Structures of Drugs and their Activities on Primary Cultures of Pediatric Solid Tumors
Current Medicinal Chemistry Fibroblast Growth Factors/Fibroblast Growth Factor Receptors as Targets for the Development of Anti-Angiogenesis Strategies
Current Pharmaceutical Design Vascular Endothelial Growth Factor and Its Receptor as Drug Targets in Hematological Malignancies
Current Drug Targets Hotspot Mutations in DICER1 Causing GLOW Syndrome-Associated Macrocephaly <i>via</i> Modulation of Specific microRNA Populations Result in the Activation of PI3K/ATK/mTOR Signaling
MicroRNA Anti-cancer and Anti-angiogenic Properties of Various Natural Pentacyclic Tri-terpenoids and Some of their Chemical Derivatives
Current Organic Chemistry Double Strand Break Repair Activities of p53 as Potential Tumor Suppressor Function Counteracting Mammary Tumor Development
Current Women`s Health Reviews Molecular Imaging of Therapeutic Potential of Reporter Probes
Current Drug Targets Mediterranean Diet, Brain and Muscle: Olive Polyphenols and Resveratrol Protection in Neurodegenerative and Neuromuscular Disorders
Current Medicinal Chemistry