Aortic heterogeneity across segments and under high fat/salt/glucose conditions at the single-cell level

Author:

He Dongxu1,Mao Aiqin1,Zheng Chang-Bo2,Kan Hao1,Zhang Ka1,Zhang Zhiming3,Feng Lei1,Ma Xin1

Affiliation:

1. Wuxi School of Medicine and School of Food Science and Technology, Jiangnan University, Wuxi 214122, China

2. School of Pharmaceutical Science and Yunnan Key Laboratory of Pharmacology for Natural Products, Kunming Medical University, Kunming 650500, China

3. School of Biotechnology, Jiangnan University, Wuxi 214122, China

Abstract

Abstract 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.

Funder

National Natural Science Foundation of China

Chang Jiang Scholars Program

Fundamental Research Funds for the Central Universities

National First-Class Discipline Program of Food Science and Technology

Foundation of Yunnan Provincial Science and Technology Department

Publisher

Oxford University Press (OUP)

Subject

Multidisciplinary

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