학술논문
Vascular dysfunction and arterial hypertension in experimental celiac disease are mediated by gut-derived inflammation and oxidative stress.
Document Type
Academic Journal
Author
Keppeler K; Center for Cardiology, University Medical Center of the Johannes Gutenberg-University, Mainz, Germany.; Pesi A; Institute of Translational Immunology (TIM), University Medical Center of the Johannes Gutenberg-University, Mainz, Germany.; Lange S; Center for Cardiology, University Medical Center of the Johannes Gutenberg-University, Mainz, Germany.; Helmstädter J; Center for Cardiology, University Medical Center of the Johannes Gutenberg-University, Mainz, Germany.; Strohm L; Center for Cardiology, University Medical Center of the Johannes Gutenberg-University, Mainz, Germany.; Ubbens H; Center for Cardiology, University Medical Center of the Johannes Gutenberg-University, Mainz, Germany.; Kuntić M; Center for Cardiology, University Medical Center of the Johannes Gutenberg-University, Mainz, Germany.; Kuntić I; Center for Cardiology, University Medical Center of the Johannes Gutenberg-University, Mainz, Germany.; Mihaliková D; Center for Cardiology, University Medical Center of the Johannes Gutenberg-University, Mainz, Germany.; Vujačić-Mirski K; Center for Cardiology, University Medical Center of the Johannes Gutenberg-University, Mainz, Germany.; Rosenberger A; Center for Cardiology, University Medical Center of the Johannes Gutenberg-University, Mainz, Germany.; Küster L; Center for Cardiology, University Medical Center of the Johannes Gutenberg-University, Mainz, Germany.; Frank C; Institute of Translational Immunology (TIM), University Medical Center of the Johannes Gutenberg-University, Mainz, Germany.; Oelze M; Center for Cardiology, University Medical Center of the Johannes Gutenberg-University, Mainz, Germany.; Finger S; Center for Thrombosis and Hemostasis (CTH), University Medical Center of the Johannes Gutenberg-University, Mainz, Germany; German Center for Cardiovascular Research (DZHK), Partner Site Rhine-Main, Mainz/Frankfurt a. M., Germany.; Zakrzewska A; Jagiellonian Centre for Experimental Therapeutics (JCET), Jagiellonian University, Krakow, Poland.; Verdu E; Farncombe Digestive Disease Center, McMaster University, Hamilton, Canada.; Wild J; Center for Cardiology, University Medical Center of the Johannes Gutenberg-University, Mainz, Germany; Center for Thrombosis and Hemostasis (CTH), University Medical Center of the Johannes Gutenberg-University, Mainz, Germany; German Center for Cardiovascular Research (DZHK), Partner Site Rhine-Main, Mainz/Frankfurt a. M., Germany.; Karbach S; Center for Cardiology, University Medical Center of the Johannes Gutenberg-University, Mainz, Germany; Center for Thrombosis and Hemostasis (CTH), University Medical Center of the Johannes Gutenberg-University, Mainz, Germany; German Center for Cardiovascular Research (DZHK), Partner Site Rhine-Main, Mainz/Frankfurt a. M., Germany.; Wenzel P; Center for Cardiology, University Medical Center of the Johannes Gutenberg-University, Mainz, Germany; Center for Thrombosis and Hemostasis (CTH), University Medical Center of the Johannes Gutenberg-University, Mainz, Germany; German Center for Cardiovascular Research (DZHK), Partner Site Rhine-Main, Mainz/Frankfurt a. M., Germany.; Wild P; Center for Cardiology, University Medical Center of the Johannes Gutenberg-University, Mainz, Germany; German Center for Cardiovascular Research (DZHK), Partner Site Rhine-Main, Mainz/Frankfurt a. M., Germany.; Leistner D; German Center for Cardiovascular Research (DZHK), Partner Site Rhine-Main, Mainz/Frankfurt a. M., Germany; Division of Cardiology, Goethe University Frankfurt, University Hospital, Department of Medicine III, Frankfurt a. M., Germany.; Münzel T; Center for Cardiology, University Medical Center of the Johannes Gutenberg-University, Mainz, Germany; German Center for Cardiovascular Research (DZHK), Partner Site Rhine-Main, Mainz/Frankfurt a. M., Germany.; Daiber A; Center for Cardiology, University Medical Center of the Johannes Gutenberg-University, Mainz, Germany; German Center for Cardiovascular Research (DZHK), Partner Site Rhine-Main, Mainz/Frankfurt a. M., Germany.; Schuppan D; Institute of Translational Immunology (TIM), University Medical Center of the Johannes Gutenberg-University, Mainz, Germany; Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.; Steven S; Center for Cardiology, University Medical Center of the Johannes Gutenberg-University, Mainz, Germany; Center for Thrombosis and Hemostasis (CTH), University Medical Center of the Johannes Gutenberg-University, Mainz, Germany; Division of Cardiology, Goethe University Frankfurt, University Hospital, Department of Medicine III, Frankfurt a. M., Germany. Electronic address: ssteven@uni-mainz.de.
Source
Publisher: Elsevier, B.V Country of Publication: Netherlands NLM ID: 101605639 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2213-2317 (Electronic) Linking ISSN: 22132317 NLM ISO Abbreviation: Redox Biol Subsets: MEDLINE
Subject
Language
English
Abstract
Aims: 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.
Methods and Results: 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.
Conclusion: 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.
Competing Interests: Declaration of competing interest All authors declared no conflicts of interest.
(Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)
Methods and Results: 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
Conclusion: 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.
Competing Interests: Declaration of competing interest All authors declared no conflicts of interest.
(Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)