Cardiovascular research, 2016-10, Vol.112 (1), p.515-525
2016
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Details
- Autor(en) / Beteiligte
- Titel
- The angiotensin II type 2 receptor activates flow-mediated outward remodelling through T cells-dependent interleukin-17 production
- Ist Teil von
- Cardiovascular research, 2016-10, Vol.112 (1), p.515-525
- Ort / Verlag
- England: Oxford University Press (OUP)
- Erscheinungsjahr
- 2016
- Quelle
- Oxford Journals 2020 Medicine
- Beschreibungen/Notizen
- The angiotensin II type 1 receptor (AT1R) through the activation of immune cells plays a key role in arterial inward remodelling and reduced blood flow in cardiovascular disorders. On the other side, flow (shear stress)-mediated outward remodelling (FMR), involved in collateral arteries growth in ischaemic diseases, allows revascularization. We hypothesized that the type 2 receptor (AT2R), described as opposing the effects of AT1R, could be involved in FMR. We studied FMR using a model of ligation of feed arteries supplying collateral pathways in the mouse mesenteric arterial bed in vivo. Seven days after ligation, diameter increased by 30% in high flow (HF) arteries compared with normal flow vessels. FMR was absent in mice lacking AT2R. At Day 2, T lymphocytes expressing AT2R were present preferentially around HF arteries. FMR did not occur in athymic (nude) mice lacking T cells and in mice treated with anti-CD3ε antibodies. AT2R activation induced interleukin-17 production by memory T cells. Treatment of nude mice or AT2R-deficient mice with interleukin-17 restored diameter enlargement in HF arteries. Interleukin-17 increased NO-dependent relaxation and matrix metalloproteinases activity, both important in FMR. Remodelling of feeding arteries in the skin flap model of ischaemia was also absent in AT2R-deficient mice and in anti-interleukin-17-treated mice. Finally, remodelling, absent in 12-month-old mice, was restored by a treatment with the AT2R non-peptidic agonist C21. AT2R-dependent interleukin-17 production by T lymphocyte is necessary for collateral artery growth and could represent a new therapeutic target in ischaemic disorders.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0008-6363eISSN: 1755-3245DOI: 10.1093/cvr/cvw172Titel-ID: cdi_hal_primary_oai_HAL_inserm_01382460v1
- Format
- –
- Schlagworte
- Age Factors, Animals, Arterial Pressure, Cancer, CD4-Positive T-Lymphocytes - drug effects, CD4-Positive T-Lymphocytes - immunology, CD4-Positive T-Lymphocytes - metabolism, Collateral Circulation, Endothelial Cells - drug effects, Endothelial Cells - metabolism, Genotype, Interleukin-17 - metabolism, Ischemia - genetics, Ischemia - immunology, Ischemia - metabolism, Ischemia - physiopathology, Life Sciences, Ligation, Macrophages - drug effects, Macrophages - metabolism, Mechanotransduction, Cellular - drug effects, Mesenteric Arteries - drug effects, Mesenteric Arteries - immunology, Mesenteric Arteries - metabolism, Mesenteric Arteries - surgery, Mesentery - blood supply, Mice, Mice, Knockout, Mice, Nude, Phenotype, RAW 264.7 Cells, Receptor, Angiotensin, Type 2 - agonists, Receptor, Angiotensin, Type 2 - deficiency, Receptor, Angiotensin, Type 2 - genetics, Receptor, Angiotensin, Type 2 - metabolism, Regional Blood Flow, Skin - blood supply, Splanchnic Circulation - drug effects, Stress, Mechanical, Time Factors, Vascular Remodeling, Vascular Resistance, Vasodilation