Macrophages preserve endothelial cell specialization in the adrenal gland to modulate aldosterone secretion and blood pressure (bulk RNA-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 induction of sub-endothelial fibrosis. To characterize the impact of macrophage VEGF-A on the whole adrenal gland, we conducted bulk RNAseq of adrenal gland from WT and VEGF/LysM mice.肾上腺皮质具有独特的组织结构，同时富含特化的血窦血管。该特殊内皮细胞表型的维持，对肾上腺的正常功能至关重要。分泌醛固酮的肾上腺球状带中，巨噬细胞与血窦毛细血管紧密毗邻。然而，稳态条件下这种巨噬细胞-内皮细胞毗邻关系的功能仍未明确。本研究证实，巨噬细胞可维持肾上腺毛细血管的特化表型，并调控醛固酮的分泌。通过结合巨噬细胞特异性敲除血管生成细胞因子血管内皮生长因子A（Vascular Endothelial Growth Factor A, VEGF-A）、单细胞转录组学与功能表型分析，我们发现：髓系细胞（包括肾上腺巨噬细胞）中VEGF-A的缺失，会导致小鼠球状带内PLVAP阳性有窗内皮细胞的特异性亚群耗竭，同时伴随基底膜IV型胶原沉积增加以及内皮下纤维化的发生。为探究巨噬细胞VEGF-A对整个肾上腺的影响，我们对野生型（WT）和VEGF/LysM小鼠的肾上腺组织开展了批量RNA测序（bulk RNAseq）。