1. Macrophages preserve endothelial cell specialization in the adrenal gland to modulate aldosterone secretion and blood pressure
- Author
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Fan, Zheng, Karakone, Mara, Nagarajan, Shunmugam, Nagy, Nadine, Mildenberger, Wiebke, Petrova, Ekaterina, Hinte, Laura Catharina, Bijnen, Mitchell, Häne, Philipp, Nelius, Eric, Chen, Jing, Ferapontova, Irina, von Meyenn, Ferdinand, Trepiccione, Francesco, Berber, Mesut, Ribas, David Penton, Eichmann, Anne, Zennaro, Maria-Christina, Takeda, Norihiko, Fischer, Jens W., Spyroglou, Ariadni, Reincke, Martin, Beuschlein, Felix, Loffing, Johannes, Greter, Melanie, and Stockmann, Christian
- Abstract
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.
- Published
- 2024
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