The Mechanisms of Gastric Mucosal Injury: Focus on Microvascular Endothelium as a Key Target

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, ischemia-reperfusion 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.

Translational Implications of the Alcohol-Metabolizing Enzymes, Including Cytochrome P450-2E1, in Alcoholic and Nonalcoholic Liver Disease

“…Liver injury, including ALD, nonalcoholic liver disease (NALD), or DILI, is often associated with suppressed vascular endothelial cell function, which is accompanied with restricted blood and oxygen supply (Doggett & Breslin, 2014;Ito, Abril, Bethea, & McCuskey, 2004;McCuskey et al, 2004;Tarnawski, Ahluwalia, & Jones, 2012). CYP2E1 also needs molecular oxygen for its catalytic activity, further lowering oxygen concentration in the pericentral regions.…”

Evaluation of the safety, gastroprotective activity and mechanism of action of standardised leaves infusion extract of Copaifera malmei Harms

“…This subsequently deprived the NO role as one of the endothelial mediators essential for mucosal defence against acute damage by decreasing gastric mucosal blood flow and gastric mucus secretion (Tarnawski et al, 2012;Júnior et al, 2014). The partial attenuation of SIECm gastroprotective effect by L-NAME suggests that replenishment of NO levels in the gastric mucosa by the SIECm is one of the possible gastroprotective mechanisms of action.…”

Does the gastroprotective action of a medicinal plant ensure healing effects? An integrative study of the biological effects of Serjania marginata Casar. (Sapindaceae) in rats

“…The gastroprotective effect of HESM was evaluated using the model of gastric ulcer induced by absolute ethanol, which induces a gastric mucosal damage associated with microcirculatory disturbances and increased vascular permeability (Tarnawski et al, 2012). Table 5 shows the gastroprotective effect of the HESM in the model of ethanol-induced gastric ulcer.…”