Macrophages preserve endothelial cell specialization in the adrenal gland to modulate aldosterone secretion and blood pressure (scRNA-Seq)

The adrenal cortex is characterized by a distinct architecture as well as a high density of specialized sinusoidal blood vessels. The preservation of this particular endothelial cell phenotype is likely vital for proper adrenal gland function. The aldosterone-producing zona glomerulosa harbors macrophages in close association with sinusoidal capillaries. However, the function of this macrophage-endothelial cell-juxtaposition in steady-state conditions is unknown. We show that macrophages preserve capillary specialization in the adrenal gland and modulate aldosterone secretion. By combining macrophage-specific deletion of the angiogenic cytokine Vascular Endothelial Growth Factor A (VEGF-A), single-cell transcriptomics and functional phenotyping, we provide evidence that loss of VEGF-A in myeloid cells, including adrenal gland macrophages depletes a specialized subset of PLVAP+ fenestrated endothelial cells in the zona glomerulosa of mice, along with increased deposition of basement membrane collagen IV and in Overall design: To characterize the impact of macrophage VEGF-A on the adrenal endothelial cell diversity, we isolated CD31+ CD45- endothelial cells from adrenal gland of WT as well as VEGF/LysM female mice at 12 weeks of age and performed single cell transcriptomics.