Hypoxia-inducible factor 1-alpha in chronic gastrointestinal ischemia

Abstract

Chronic gastrointestinal ischemia (CGI) is the result of decreased mucosal perfusion. Typical histological characteristics are lacking which hamper its early diagnosis. Hypoxia-inducible factor-1alpha (HIF-1alpha) is expressed under acute hypoxia. We investigated HIF-1alpha expression in chronic ischemic and inflammatory conditions of the human gastrointestinal (GI) tract. Immunohistochemical expression of HIF-1alpha was analyzed in 61 patients, including patients with CGI, Helicobacter pylori gastritis, ischemic colitis (IC), infectious colitis, and inflammatory bowel disease (IBD), and 22 controls. HIF-1alpha expression in >10 % of the cells was regarded as positive staining, and expression <10 % of the cells was considered as negative staining. In the upper GI tract, HIF-1alpha expression was found in 5/20 CGI patients, but not in controls (p = 0.08). The sensitivity and specificity of HIF-1alpha expression for diagnosing CGI were 25 and 84%, respectively. In the lower GI tract, HIF-1alpha was expressed in all patients with IC and infectious colitis and in a majority of IBD patients as well as in 7/12 controls. The sensitivity and specificity of HIF-1alpha for diagnosing IC were 100 and 51%, respectively. HIF-1alpha expression was more often (p = 0.02) observed in patients with histological signs of inflammation in the lower GI tract. HIF-1alpha is expressed in acute and chronic ischemic tissue, but also in normal colon tissue and inflammatory disorders.