Relationship between inflammation and tissue hypoxia in a mouse model of chronic colitis

Carter, Patsy R.; Yadav, Amit Singh; Watts, Megan N.; Zhang, Songlin; Kosloski-Davidson, Melissa; Grisham, Matthew B.

doi:10.1002/ibd.21423

Cited by 17 publications

(16 citation statements)

References 15 publications

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“…We also showed concomitant upregulation of hypoxia-related transcription factors HIF-1a and Egr-1. Our data are in agreement with others on the models of UC induced by adoptive transfer of IL-10 À/À CD4 þ T cells into RAG À/À mice 40 or TNBS in mice.…”

Section: Endothelial Damage In Ulcerative Colitissupporting

confidence: 93%

Early endothelial damage and increased colonic vascular permeability in the development of experimental ulcerative colitis in rats and mice

Tolstanova

Deng

French

et al. 2012

Laboratory Investigation

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The role of endothelial damage and increased vascular permeability (VP) in the pathogenesis of ulcerative colitis (UC) has not been investigated. We examined using functional, morphologic, and molecular biologic studies whether and to what extent the endothelial barrier dysfunction precedes enhanced epithelial permeability (EP) and the development of mucosal lesions during the early stages of experimental UC. We showed that in rats with iodoacetamide (IA)-induced UC increased colonic VP occurs early (ie, 2.6-fold increase at 15 min, Po0.01) preceding changes in epithelial barrier permeability. EP was unchanged at 15 and 30 min after IA administration and was increased 1.9-fold at 1 h and 6.7-fold at 2 h (both Po0.001) after IA. In the dextran sodium sulfate-induced slowly developing UC, colonic VP was significantly increased in 2 days (Po0.05) and EP only in 4 days (Po0.05). Mucosal endothelial injury led to hypoxia (Po0.05) of colonic surface epithelial cells 30 min after IA administration that was associated with increased expressions of transcription factors hypoxia-inducible factor-1a and early growth response-1. Electron and light microscopy demonstrated areas of colonic mucosa with perivascular edema covered by intact layer of surface epithelial cells in both rat and mouse models of UC. This is the first demonstration in four models of UC that endothelial damage, increased colonic VP, perivascular edema, and epithelial hypoxia precede epithelial barrier dysfunction that is followed by erosions, ulceration, and inflammation in UC. KEYWORDS: endothelial damage; epithelial permeability; hypoxia; inflammatory bowel disease; ulcerative colitis; vascular permeability Ulcerative colitis (UC) is characterized by chronic, recurrent ulcers and inflammation of the colonic mucosa. It has been postulated that impaired epithelial barrier function, resulting in penetration of bacteria and other antigens into the mucosa, is one of the major factors of UC pathogenesis.

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Section: Endothelial Damage In Ulcerative Colitissupporting

confidence: 93%

Early endothelial damage and increased colonic vascular permeability in the development of experimental ulcerative colitis in rats and mice

Tolstanova

Deng

French

et al. 2012

Laboratory Investigation

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“…Histological analysis of hypoxia-dependent pimonidazole retention revealed the development of transmural hypoxia in CS-exposed mice, as opposed to the epithelial localization of hypoxia in the normal gut (24,31). In support of this role for smoking-associated GIT hypoxia, laser doppler analysis of smokers demonstrated a decrease in rectal blood flow within 30 minutes of smoking (49).…”

Section: Discussionmentioning

confidence: 93%

“…To investigate whether increased systemic and colon tissue hypoxia was associated with experimental COPD, we employed the pimanidazole-based dye, hypoxyprobe, which forms immunochemically detectable adducts with thiol-containing amino acids in hypoxic tissues (partial pressure of oxygen [pO 2 ] < 10 mm Hg) (30). In colons from normal air-exposed groups, tissue hypoxia was restricted to the luminal epithelial layer (Figure 3, A-C), as previously described (24,31). In contrast, colonic tissue from CS-exposed groups exhibited an increased amount of total hypoxyprobe signal, which was present throughout the mucosal layer, as opposed to being restricted exclusively to the lumenal epithelium.…”

Section: Resultsmentioning

confidence: 99%

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Chronic cigarette smoke exposure induces systemic hypoxia that drives intestinal dysfunction

Fricker¹,

Goggins²,

Mateer³

et al. 2018

JCI Insight

119

103

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“…However, despite the arteriolar constriction and lower blood flow rates in individual vessels, overall blood flow in the colon is only marginally reduced as a consequence of an approximate doubling of vascular density (81,191,193,304,341). A subset of mice in the T-cell transfer model exhibited a significantly reduced overall blood flow, which was accompanied by mucosal hypoxia and mild inflammation (192). The hyperemic response noted in some animal models of colitis has been linked to increased eNOS, but not iNOS, activity in the colonic mucosa, with eNOS inhibition yielding a significant attenuation of the colitis-induced hyperemic response (384).…”

Section: Vascular Responses To Chronic Inflammationmentioning

confidence: 94%

The Gastrointestinal Circulation: Physiology and Pathophysiology

Granger

Holm

Kvietys

2015

Comprehensive Physiology

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The gastrointestinal (GI) circulation receives a large fraction of cardiac output and this increases following ingestion of a meal. While blood flow regulation is not the intense phenomenon noted in other vascular beds, the combined responses of blood flow, and capillary oxygen exchange help ensure a level of tissue oxygenation that is commensurate with organ metabolism and function. This is evidenced in the vascular responses of the stomach to increased acid production and in intestine during periods of enhanced nutrient absorption. Complimenting the metabolic vasoregulation is a strong myogenic response that contributes to basal vascular tone and to the responses elicited by changes in intravascular pressure. The GI circulation also contributes to a mucosal defense mechanism that protects against excessive damage to the epithelial lining following ingestion of toxins and/or noxious agents. Profound reductions in GI blood flow are evidenced in certain physiological (strenuous exercise) and pathological (hemorrhage) conditions, while some disease states (e.g., chronic portal hypertension) are associated with a hyperdynamic circulation. The sacrificial nature of GI blood flow is essential for ensuring adequate perfusion of vital organs during periods of whole body stress. The restoration of blood flow (reperfusion) to GI organs following ischemia elicits an exaggerated tissue injury response that reflects the potential of this organ system to generate reactive oxygen species and to mount an inflammatory response. Human and animal studies of inflammatory bowel disease have also revealed a contribution of the vasculature to the initiation and perpetuation of the tissue inflammation and associated injury response.

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Relationship between inflammation and tissue hypoxia in a mouse model of chronic colitis

Cited by 17 publications

References 15 publications

Early endothelial damage and increased colonic vascular permeability in the development of experimental ulcerative colitis in rats and mice

Early endothelial damage and increased colonic vascular permeability in the development of experimental ulcerative colitis in rats and mice

Chronic cigarette smoke exposure induces systemic hypoxia that drives intestinal dysfunction

The Gastrointestinal Circulation: Physiology and Pathophysiology

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