Deletion of the myeloid endothelin-B receptor confers long-term protection from angiotensin II-mediated kidney, eye and vessel injury
| Autor: | Pierre-Louis Tharaux, Véronique Baudrie, Christophe Roubeix, Anna Chipont, Léa Guyonnet, Matthew A. Bailey, Tariq E. Farrah, Alicja Czopek, David C. Kluth, David J. Webb, Philippe Bonnin, Olivia Lenoir, Florian Sennlaub, Neeraj Dhaun |
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| Přispěvatelé: | Paris-Centre de Recherche Cardiovasculaire (PARCC (UMR_S 970/ U970)), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), University of Edinburgh, Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut de la Vision, Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Gestionnaire, Hal Sorbonne Université, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS) |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty Myeloid hypertension [SDV]Life Sciences [q-bio] 030232 urology & nephrology Inflammation Blood Pressure Kidney MESH: Hypertension organ injury 03 medical and health sciences Mice 0302 clinical medicine Internal medicine medicine Animals MESH: Animals Receptor MESH: Mice MESH: Endothelins business.industry Angiotensin II Endothelins Glomerulosclerosis MESH: Blood Pressure MESH: Kidney medicine.disease Receptor Endothelin B MESH: Receptor Endothelin B macrophages [SDV] Life Sciences [q-bio] 030104 developmental biology Endocrinology Blood pressure medicine.anatomical_structure Basic Research Nephrology MESH: Angiotensin II medicine.symptom business Endothelin receptor endothelin |
| Zdroj: | Kidney International Kidney International, Nature Publishing Group, 2020, 98 (5), pp.1193-1209. ⟨10.1016/j.kint.2020.05.042⟩ Kidney International, 2020, 98 (5), pp.1193-1209. ⟨10.1016/j.kint.2020.05.042⟩ |
| ISSN: | 1523-1755 0085-2538 |
| DOI: | 10.1016/j.kint.2020.05.042⟩ |
| Popis: | The endothelin system may be an important player in hypertensive end-organ injury as endothelin-1 increases blood pressure and is pro-inflammatory. The immune system is emerging as an important regulator of blood pressure and we have shown that the early hypertensive response to angiotensin-II infusion was amplified in mice deficient of myeloid endothelin-B (ETB) receptors (LysM-CreEdnrblox/lox). Hypothesizing that these mice would display enhanced organ injury, we gave angiotensin-II to LysM-CreEdnrblox/lox and littermate controls (Ednrblox/lox) for six weeks. Unexpectedly, LysM-CreEdnrblox/lox mice were significantly protected from organ injury, with less proteinuria, glomerulosclerosis and inflammation of the kidney compared to controls. In the eye, LysM-CreEdnrblox/lox mice had fewer retinal hemorrhages, less microglial activation and less vessel rarefaction. Cardiac remodeling and dysfunction were similar in both groups at week six but LysM-CreEdnrblox/lox mice had better endothelial function. Although blood pressure was initially higher in LysM-CreEdnrblox/lox mice, this was not sustained. A natriuretic switch at about two weeks, due to enhanced ETB signaling in the kidney, induced a hypertensive reversal. By week six, blood pressure was lower in LysM-CreEdnrblox/lox mice than in controls. At six weeks, macrophages from LysM-CreEdnrblox/lox mice were more anti-inflammatory and had greater phagocytic ability compared to the macrophages of Ednrblox/lox mice. Thus, myeloid cell ETB receptor signaling drives this injury both through amplifying hypertension and by inflammatory polarization of macrophages. Graphical abstract |
| Databáze: | OpenAIRE |
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