Single cell transcriptomic analysis identifies novel vascular smooth muscle subsets under high hydrostatic pressure
Single cell transcriptomic analysis identifies novel vascular smooth muscle subsets under high hydrostatic pressure
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单细胞转录组分析鉴定高静水压下新的血管平滑肌亚群
DOI：
10.1007/s11427-020-1852-x
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发表时间：
2021-01-21
影响因子：
9.1
通讯作者：
Cai, Jun
中科院分区：
文献类型：
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作者：
Chen, Zhenzhen;Zhang, Haizeng;Cai, Jun
尽管一些共同危险因素和血流动力学改变参与了高血压的进展，但它们的直接生物力学效应尚不清楚。在这里，我们构建了一个模拟持续高血压的高静水压细胞培养系统，并通过单细胞转录组分析鉴定了新的人主动脉平滑肌细胞(HASMC)的分子分类。经基因差异表达和基因本体富集化分析，HASMCs在100 mm Hg(相当于正常人血压)或200 mm Hg(相当于高血压)的静水压力下作用48h，可形成6个不同的血管SMC簇。特别是，以CXCL2、CXCL3和CCL2为标记物的HASMC亚群和以AKR1C2、AKR1C3、SERPINF1为标记物的内皮功能抑制亚群被鉴定为炎症亚群。炎症亚群促进CXCL2&3和CCL2趋化因子的表达和分泌，触发单核细胞迁移；内皮功能抑制亚群分泌SERPINF1，促进前列腺素F2α生成，抑制血管生成。高血压患者和实验性高血压动物模型动脉中膜中这两种VSMC亚群的表达均显著增加。总而言之，我们发现高静水压力直接将VSMCs分为两个新的亚群，促进或加重内皮功能障碍，从而促进心血管疾病的发病。
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.