The aorta, with ascending, arch, thoracic and abdominal segments, responds to the heartbeat, senses metabolites and distributes blood to all parts of the body. However, the heterogeneity across aortic segments and how metabolic pathologies change it are not known. Here, a total of 216 612 individual cells from the ascending aorta, aortic arch, and thoracic and abdominal segments of mouse aortas under normal conditions or with high blood glucose levels, high dietary salt, or high fat intake were profiled using single-cell RNA sequencing. We generated a compendium of 10 distinct cell types, mainly endothelial (EC), smooth muscle (SMC), stromal and immune cells. The distributions of the different cells and their intercommunication were influenced by the hemodynamic microenvironment across anatomical segments, and the spatial heterogeneity of ECs and SMCs may contribute to differential vascular dilation and constriction that were measured by wire myography. Importantly, the composition of aortic cells, their gene expression profiles and their regulatory intercellular networks broadly changed in response to high fat/salt/glucose conditions. Notably, the abdominal aorta showed the most dramatic changes in cellular composition, particularly involving ECs, fibroblasts and myeloid cells with cardiovascular risk factor-related regulons and gene expression networks. Our study elucidates the nature and range of aortic cell diversity, with implications for the treatment of metabolic pathologies.

中文翻译：

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单细胞水平上跨节段和高脂肪/盐/葡萄糖条件下的主动脉异质性


主动脉包括升段、弓段、胸段和腹段，对心跳做出反应，感知代谢物并将血液分配到身体的各个部位。然而，主动脉节段之间的异质性以及代谢病理学如何改变它尚不清楚。在这里，使用单细胞 RNA 对正常条件下或高血糖水平、高盐饮食或高脂肪摄入下小鼠主动脉的升主动脉、主动脉弓以及胸腹段的总共 216 612 个单个细胞进行了分析。测序。我们生成了 10 种不同细胞类型的纲要，主要是内皮细胞 (EC)、平滑肌细胞 (SMC)、基质细胞和免疫细胞。不同细胞的分布及其相互通讯受到解剖部分的血流动力学微环境的影响，EC和SMC的空间异质性可能有助于通过线肌动描记术测量血管扩张和收缩的差异。重要的是，主动脉细胞的组成、基因表达谱和细胞间调节网络在高脂肪/盐/葡萄糖条件下发生了广泛的变化。值得注意的是，腹主动脉的细胞组成发生了最显着的变化，特别是涉及具有心血管危险因素相关调节子和基因表达网络的内皮细胞、成纤维细胞和骨髓细胞。我们的研究阐明了主动脉细胞多样性的性质和范围，对代谢病理学的治疗具有影响。