T Cell-Derived IL-17A Induces Vascular Dysfunction via Perivascular Fibrosis Formation and Dysregulation of ⋅NOcGMP Signaling
Joint Authors
Oelze, Matthias
Daiber, Andreas
Münzel, Thomas
Li, Huige
Schüler, Rebecca
Efentakis, Panagiotis
Wild, Johannes
Lagrange, Jérémy
Garlapati, Venkata
Molitor, Michael
Kossmann, Sabine
Stamm, Paul
Schäfer, Katrin
Waisman, Ari
Karbach, Susanne Helena
Wenzel, Philip
Source
Oxidative Medicine and Cellular Longevity
Issue
Vol. 2019, Issue 2019 (31 Dec. 2019), pp.1-15, 15 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2019-07-18
Country of Publication
Egypt
No. of Pages
15
Main Subjects
Abstract EN
Aims.
The neutrophil recruiting cytokine Interleukin-17A (IL-17A) is a key component in vascular dysfunction and arterial hypertension.
Moreover, IL-17A has a central role for the vascular infiltration of myeloid cells into the arterial wall in Angiotensin II-induced vascular inflammation.
The intention of our study was to analyze the impact of T cell-derived IL-17A on hypertension, vascular function, and inflammation.
Methods and Results.
Chronic IL-17A overexpression in T cells (CD4-IL-17Aind/+ mice) resulted in elevated reactive oxygen species in the peripheral blood and a significant vascular dysfunction compared to control mice.
The vascular dysfunction seen in the CD4-IL-17Aind/+ mice was only accompanied by a modest and nonsignificant accumulation of inflammatory cells within the vessel wall.
Therefore, infiltrating myeloid cells did not serve as an explanation of the vascular dysfunction seen in a chronic IL-17A-driven mouse model.
In addition to vascular dysfunction, CD4-IL-17Aind/+ mice displayed vascular fibrosis with highly proliferative fibroblasts.
This fibroblast proliferation was induced by exposure to IL-17A as confirmed by in vitro experiments with primary murine fibroblastic cells.
We also found that the ⋅NO/cGMP pathway was downregulated in the vasculature of the CD4-IL-17Aind/+ mice, while levels of protein tyrosine kinase 2 (PYK2), an oxidative stress-triggered process associated with T cell activation, were upregulated in the perivascular fat tissue (PVAT).
Conclusions.
Our data demonstrate that T cell-derived IL-17A elicits vascular dysfunction by mediating proliferation of fibroblasts and subsequent vascular fibrosis associated with PYK2 upregulation.
American Psychological Association (APA)
Schüler, Rebecca& Efentakis, Panagiotis& Wild, Johannes& Lagrange, Jérémy& Garlapati, Venkata& Molitor, Michael…[et al.]. 2019. T Cell-Derived IL-17A Induces Vascular Dysfunction via Perivascular Fibrosis Formation and Dysregulation of ⋅NOcGMP Signaling. Oxidative Medicine and Cellular Longevity،Vol. 2019, no. 2019, pp.1-15.
https://search.emarefa.net/detail/BIM-1204760
Modern Language Association (MLA)
Schüler, Rebecca…[et al.]. T Cell-Derived IL-17A Induces Vascular Dysfunction via Perivascular Fibrosis Formation and Dysregulation of ⋅NOcGMP Signaling. Oxidative Medicine and Cellular Longevity No. 2019 (2019), pp.1-15.
https://search.emarefa.net/detail/BIM-1204760
American Medical Association (AMA)
Schüler, Rebecca& Efentakis, Panagiotis& Wild, Johannes& Lagrange, Jérémy& Garlapati, Venkata& Molitor, Michael…[et al.]. T Cell-Derived IL-17A Induces Vascular Dysfunction via Perivascular Fibrosis Formation and Dysregulation of ⋅NOcGMP Signaling. Oxidative Medicine and Cellular Longevity. 2019. Vol. 2019, no. 2019, pp.1-15.
https://search.emarefa.net/detail/BIM-1204760
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1204760