Medizinische Universität Graz - Research portal
Selected Publication:
SHR Neuro Cancer Cardio Lipid Metab Microb
Spencer, AU; Yang, H; Haxhija, EQ; Wildhaber, BE; Greenson, JK; Teitelbaum, DH.
Reduced severity of a mouse colitis model with angiotensin converting enzyme inhibition.
Dig Dis Sci. 2007; 52(4):1060-1070
Doi: 10.1007/s10620-006-9124-2
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- Co-authors Med Uni Graz
- Haxhija Emir
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- Abstract:
- Ulcerative colitis is characterized by elevated rates of epithelial cell apoptosis, and an up-regulation of pro-apoptotic cytokines including tumor necrosis factor alpha (TNF-alpha). Recently, angiotensin converting enzyme (ACE) has been shown to promote apoptosis. In addition, pharmacologic ACE inhibition (ACE-I) both prevents apoptosis and reduces TNF-alpha expression in vitro. We hypothesized that ACE-I, using enalaprilat, would decrease colonic epithelial cell apoptosis and reduce colitis severity in the dextran sulfate sodium (DSS)-induced colitis model in mice. We assessed the severity of colitis, and colonic epithelial cell apoptosis, after administration of DSS. Mice were given either daily ACE-I treatment or daily placebo. ACE-I treatment markedly improved clinical outcomes. In addition, ACE-I treatment significantly reduced the maximum histopathologic colitis grade. ACE-I also dramatically reduced the epithelial apoptotic rate. To investigate the mechanism by which ACE-I reduced apoptosis; we measured TNF-alpha, Bcl-2, and Bax expression. TNF-alpha mRNA was significantly lower with ACE-I treatment compared to placebo at every time point, as was the ratio of Bax to Bcl-2. We conclude that ACE-I reduces the severity of DSS-induced colitis and reduces epithelial cell apoptosis.
- Find related publications in this database (using NLM MeSH Indexing)
- Angiotensin-Converting Enzyme Inhibitors - pharmacology
- Animals - pharmacology
- Apoptosis - drug effects
- Colitis - chemically induced
- Colon - blood supply
- Dextran Sulfate - blood supply
- Enalaprilat - pharmacology
- Epithelial Cells - drug effects
- Flow Cytometry - drug effects
- Intestinal Mucosa - blood supply
- Male - blood supply
- Mice - blood supply
- Mice, Inbred C57BL - blood supply
- Peptidyl-Dipeptidase A - metabolism
- Proto-Oncogene Proteins c-bcl-2 - metabolism
- Regional Blood Flow - drug effects
- Tumor Necrosis Factor-alpha - metabolism
- bcl-2-Associated X Protein - metabolism
- Find related publications in this database (Keywords)
- dextran sulfate sodium
- ulcerative colitis
- angiotensin converting enzyme (ACE)
- tumor necrosis factor-alpha
- apoptosis
- ACE inhibitor