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Single cell transcriptomic analysis identifies novel vascular smooth muscle subsets under high hydrostatic pressure

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Abstract

Although some co-risk factors and hemodynamic alterations are involved in hypertension progression, their direct biomechanical effects are unclear. Here, we constructed a high-hydrostatic-pressure cell-culture system to imitate constant hypertension and identified novel molecular classifications of human aortic smooth muscle cells (HASMCs) by single-cell transcriptome analysis. Under 100-mmHg (analogous to healthy human blood pressure) or 200-mmHg (analogous to hypertension) hydrostatic pressure for 48 h, HASMCs showed six distinct vascular SMC (VSMC) clusters according to differential gene expression and gene ontology enrichment analysis. Especially, two novel HASMC subsets were identified, named the inflammatory subset, with CXCL2, CXCL3 and CCL2 as markers, and the endothelial-function inhibitory subset, with AKR1C2, AKR1C3, SERPINF1 as markers. The inflammatory subset promoted CXCL2&3 and CCL2 chemokine expression and secretion, triggering monocyte migration; the endothelial-function inhibitory subset secreted SERPINF1 and accelerated prostaglandin F2α generation to inhibit angiogenesis. The expression of the two VSMC subsets was greatly increased in arterial media from patients with hypertension and experimental animal models of hypertension. Collectively, we identified high hydrostatic pressure directly driving VSMCs into two new subsets, promoting or exacerbating endothelial dysfunction, thereby contributing to the pathogenesis of cardiovascular diseases.

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Acknowledgements

This work was supported by the National Key Research and Development Program of China (2018YFC1312703), CAMS Innovation Fund for Medical Sciences (CIFMS, 2016-12M1-006), the National Natural Science Foundation of China (81630014, 81825002, 81800367, 81870318, 81670379), and Beijing Outstanding Young Scientist Program (BJJWZYJH01201910023029).

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Authors and Affiliations

  1. Hypertension Center, Department of Cardiac Surgery, Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, State Key Laboratory of Cardiovascular Disease, National Center for Cardiovascular Diseases, Beijing, 100191, China

    Zhenzhen Chen, Haizeng Zhang, Changting Cui, Shuangyue Li, Wenjie Wang, Yue Deng, Qiannan Gao, Lu Wang, Yan Yang, Bin Geng & Jun Cai

  2. Novogene Bioinformatics Technology Co., Ltd., Beijing, 100015, China

    Yingnan Bai, Wei Qi & Lijun Zhang

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  1. Zhenzhen Chen
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  2. Haizeng Zhang
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Chen, Z., Zhang, H., Bai, Y. et al. Single cell transcriptomic analysis identifies novel vascular smooth muscle subsets under high hydrostatic pressure. Sci. China Life Sci. 64, 1677–1690 (2021). https://doi.org/10.1007/s11427-020-1852-x

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