Abstract 154: Endothelial Dysfunction In Experimental Celiac Disease Is Mediated By Gut-Derived Vascular Inflammation And Oxidative Stress

Objective: Celiac disease (CeD) is an autoimmune enteropathy triggered by dietary gluten, with a prevalence around 1%. Since many patients show heterogeneous symptoms, it is vastly underdiagnosed and yet without any treatment option besides lifelong gluten restriction. Vascular function in CeD patients compared to healthy controls has been assessed and hypothesized CeD as a cardiovascular risk factor. Herewith we aimed to explore the cardiovascular effects of CeD in a murine model, with special emphasis on endothelial dysfunction, vascular inflammation, and oxidative stress, known triggers for cardiovascular disease. Methods: NOD.DQ8 mice were raised on a zein-based, gluten-free diet. During the experiment, mice received gavage with peptic-tryptic digest of gliadin and were switched to a gluten-containing diet (Gliadin group). A control group (Zein group) was continued on gluten-free diet and received accordingly digested zein. Results: Blood pressure measurements revealed arterial hypertension in the Gliadin group. Endothelium-dependent relaxation was impaired in the Gliadin group compared to Zein, whereas no change in endothelium-independent was observed, tested by isometric tension recordings. Pro-inflammatory genes, like Tnfa and Nox2 were upregulated in the Gliadin group measured by quantitative rtPCR in aortic and intestinal tissue. Infiltration by intraepithelial T-lymphocytes into the epithelium of the small intestine was shown by IHC. In cardiac tissue, gliadin-treatment increased the oxidative stress parameters 3-nitrotyrosine and 4-hydroxy-2-nonenal shown in dot blots. To investigate the inflammatory link between gut and the cardiovascular system plasma proteomics were performed and revealed elevated levels of IL-17A. Conclusion: CeD is a cardiovascular risk factor. However, the mechanism remains unresolved. In a mouse model, we demonstrate that gluten treatment elevates blood pressure and impairs vascular function. Intestinal inflammation conveys to the cardiovascular system, leads to oxidative stress, and thereby impairs endothelial function. A potential mediator might be IL-17A, whose role in other autoimmunity-based cardiovascular risk factors (e.g., psoriasis) has already been demonstrated.