Vascular dysfunction and arterial hypertension in experimental celiac disease are mediated by gut-derived inflammation and oxidative stress

• DOI: 10.1016/j.redox.2024.103071
• Publication Date: 2024-02-08T16:58:56Z
• Authors: Karin Keppeler; Aline Pesi; Simon Lange; Johanna Helmstädter; Lea Strohm; Henning Ubbens; Marin Kuntić; Ivana Kuntić; Dominika Mihaliková; Ksenija Vujačić-M...; Alexandra Rosenbe...; Leonie Küster; Charlotte Frank; Matthias Oelze; Stefanie Finger; Agnieszka Zakrzewska; Elena Verdu; Johannes Wild; Susanne Karbach; Philip Wenzel; Philipp Wild; David Leistner; Thomas Münzel; Andreas Daiber; Detlef Schuppan; Sebastian Steven
• Keywords: Arterial hypertension; arterial hypertension; Medicine (General); Glutens; QH301-705.5; interleukin-17A; endothelial dysfunction; Mice; 03 medical and health sciences; R5-920; Mice, Inbred NOD; oxidative stress; vascular inflammation; Celiac disease; Animals; Endothelial dysfunction; Biology (General); Vascular inflammation; Interleukin-17A; Inflammation; 0303 health sciences; Interleukin-17; Celiac Disease; Oxidative Stress; Oxidative stress; Hypertension; celiac disease; Research Paper

We examined the cardiovascular effects of celiac disease (CeD) in a humanized mouse model, with a focus on vascular inflammation, endothelial dysfunction, and oxidative stress.NOD.DQ8 mice genetically predisposed to CeD were subjected to a diet regime and oral gavage to induce the disease (gluten group vs. control). We tested vascular function, confirmed disease indicators, and evaluated inflammation and oxidative stress in various tissues. Plasma proteome profiling was also performed. CeD markers were confirmed in the gluten group, indicating increased blood pressure and impaired vascular relaxation. Pro-inflammatory genes were upregulated in this group, with increased CD11b+ myeloid cell infiltration and oxidative stress parameters observed in aortic and heart tissue. However, heart function remained unaffected. Plasma proteomics suggested the cytokine interleukin-17A (IL-17A) as a link between gut and vascular inflammation. Cardiovascular complications were reversed by adopting a gluten-free diet.Our study sheds light in the heightened cardiovascular risk associated with active CeD, revealing a gut-to-cardiovascular inflammatory axis potentially mediated by immune cell infiltration and IL-17A. These findings augment our understanding of the link between CeD and cardiovascular disease providing clinically relevant insight into the underlying mechanism. Furthermore, our discovery that cardiovascular complications can be reversed by a gluten-free diet underscores a critical role for dietary interventions in mitigating cardiovascular risks associated with CeD.