Macrophages preserve endothelial cell specialization in the adrenal gland to modulate aldosterone secretion and blood pressure.

Autor:	Fan Z; University of Zurich, Institute of Anatomy, 8057 Zurich, Switzerland. Electronic address: zheng.fan@anatomy.uzh.ch., Karakone M; University of Zurich, Institute of Anatomy, 8057 Zurich, Switzerland., Nagarajan S; University of Zurich, Institute of Anatomy, 8057 Zurich, Switzerland., Nagy N; Division of Infectious Diseases and Geographic Medicine, Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA., Mildenberger W; University of Zurich, Institute for Experimental Immunology, 8057 Zurich, Switzerland., Petrova E; University of Zurich, Institute for Experimental Immunology, 8057 Zurich, Switzerland., Hinte LC; Laboratory of Nutrition and Metabolic Epigenetics, Institute for Food, Nutrition and Health, Department of Health Sciences and Technology, ETH Zurich, Zurich, Switzerland., Bijnen M; University of Zurich, Institute for Experimental Immunology, 8057 Zurich, Switzerland., Häne P; University of Zurich, Institute for Experimental Immunology, 8057 Zurich, Switzerland., Nelius E; University of Zurich, Institute of Anatomy, 8057 Zurich, Switzerland., Chen J; University of Zurich, Institute of Anatomy, 8057 Zurich, Switzerland., Ferapontova I; University of Zurich, Institute of Anatomy, 8057 Zurich, Switzerland., von Meyenn F; Laboratory of Nutrition and Metabolic Epigenetics, Institute for Food, Nutrition and Health, Department of Health Sciences and Technology, ETH Zurich, Zurich, Switzerland., Trepiccione F; Department of Translational Medical Sciences, University of Campania Luigi Vanvitelli, Naples, Italy., Berber M; University of Zurich, Institute of Anatomy, 8057 Zurich, Switzerland., Ribas DP; Electrophysiology Facility (e-phac), Department of Molecular Life Sciences, University of Zurich (UZH), 8057 Zürich, Switzerland., Eichmann A; Cardiovascular Research Center and Department of Cellular and Molecular Physiology, Yale University School of Medicine, New Haven, CT, USA., Zennaro MC; INSERM U970, Paris Cardiovascular Research Center, Paris, France., Takeda N; Department of Cardiovascular Medicine, Graduate School of Medicine, The University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo, Japan., Fischer JW; Institute of Pharmacology and Clinical Pharmacology, Medical Faculty, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany., Spyroglou A; Klinik für Endokrinologie, Diabetologie, und Klinische Ernährung, UniversitätsSpital Zürich (USZ) and UZH, Raemistrasse 100, 8091 Zurich, Switzerland; Medizinische Klinik und Poliklinik IV, Ludwig-Maximilians-University (LMU), Munich, Germany., Reincke M; Klinik für Endokrinologie, Diabetologie, und Klinische Ernährung, UniversitätsSpital Zürich (USZ) and UZH, Raemistrasse 100, 8091 Zurich, Switzerland., Beuschlein F; Klinik für Endokrinologie, Diabetologie, und Klinische Ernährung, UniversitätsSpital Zürich (USZ) and UZH, Raemistrasse 100, 8091 Zurich, Switzerland; Medizinische Klinik und Poliklinik IV, Ludwig-Maximilians-University (LMU), Munich, Germany., Loffing J; University of Zurich, Institute of Anatomy, 8057 Zurich, Switzerland., Greter M; University of Zurich, Institute for Experimental Immunology, 8057 Zurich, Switzerland., Stockmann C; University of Zurich, Institute of Anatomy, 8057 Zurich, Switzerland; INSERM U970, Paris Cardiovascular Research Center, Paris, France. Electronic address: christian.stockmann@anatomy.uzh.ch.
Jazyk:	angličtina
Zdroj:	Cell reports [Cell Rep] 2024 Jul 23; Vol. 43 (7), pp. 114395. Date of Electronic Publication: 2024 Jun 26.
DOI:	10.1016/j.celrep.2024.114395
Abstrakt:	Macrophages play crucial roles in organ-specific functions and homeostasis. In the adrenal gland, macrophages closely associate with sinusoidal capillaries in the aldosterone-producing zona glomerulosa. We demonstrate that macrophages preserve capillary specialization and modulate aldosterone secretion. Using macrophage-specific deletion of VEGF-A, single-cell transcriptomics, and functional phenotyping, we found that the loss of VEGF-A depletes PLVAP + fenestrated endothelial cells in the zona glomerulosa, leading to increased basement membrane collagen IV deposition and subendothelial fibrosis. This results in increased aldosterone secretion, called "haptosecretagogue" signaling. Human aldosterone-producing adenomas also show capillary rarefaction and basement membrane thickening. Mice with myeloid cell-specific VEGF-A deletion exhibit elevated serum aldosterone, hypokalemia, and hypertension, mimicking primary aldosteronism. These findings underscore macrophage-to-endothelial cell signaling as essential for endothelial cell specialization, adrenal gland function, and blood pressure regulation, with broader implications for other endocrine organs. Competing Interests: Declaration of interests The authors declare no competing interests. (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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