Macrophages preserve endothelial cell specialization in the adrenal gland to modulate aldosterone secretion and blood pressure.
Cell Rep
; 43(7): 114395, 2024 Jul 23.
Article
em En
| MEDLINE
| ID: mdl-38941187
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.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Pressão Sanguínea
/
Glândulas Suprarrenais
/
Células Endoteliais
/
Aldosterona
/
Macrófagos
Limite:
Animals
/
Humans
/
Male
Idioma:
En
Revista:
Cell Rep
Ano de publicação:
2024
Tipo de documento:
Article
País de publicação:
Estados Unidos