Abstract
Elevated blood pressure caused by excessive salt intake is common and associated with cardiovascular diseases in most countries. However, the composition and responses of vascular cells in the progression of hypertension have not been systematically described. We performed single-cell RNA sequencing on the aortic arch from C57BL/6J mice fed a chow/high-salt diet. We identified 19 distinct cell populations representing 12 lineages, including smooth muscle cells (SMCs), fibroblasts, endothelial cells (ECs), B cells, and T cells. During the progression of hypertension, the proportion of three SMC subpopulations, two EC subpopulations, and T cells increased. In two EC clusters, the expression of reactive oxygen species-related enzymes, collagen and contractility genes was upregulated. Gene set enrichment analysis showed that three SMC subsets underwent endothelial-to-mesenchymal transition. We also constructed intercellular networks and found more frequent cell communication among aortic cells in hypertension and that some signaling pathways were activated during hypertension. Finally, joint public genome-wide association study data and our single-cell RNA-sequencing data showed the expression of hypertension susceptibility genes in ECs, SMCs, and fibroblasts and revealed 21 genes involved in the initiation and development of high-salt-induced hypertension. In conclusion, our data illustrate the transcriptional landscape of vascular cells in the aorta associated with hypertension and reveal dramatic changes in cell composition and intercellular communication during the progression of hypertension.
Highlights
For 99.2% of the global adult population, individual salt (NaCl) intake exceeds the maximum limit recommended by the World Health Organization[1,2]
We generated clusterspecific marker genes to define the identity of each cluster, including smooth muscle cells (SMCs) (Myh[11]; Acta[2]; Tagln), fibroblasts (Pdgfa; Col1a1; Mmp2), endothelial cells (ECs) (Tie[1]; Pecam[1]; Cdh5), B cells (Ly6d; Cd79a; Cd79b), monocytes (Cd209a; Gm2a; Lgals3), T cells a chow diet
We identified the genes encoding C1q And TNF Related 9 (C1qtnf9), von Willebrand factor, and Prospero homeobox 1 (Prox1) as the key marker genes for clusters EC 1, EC 2, and EC 3 (Fig. 2c)
Summary
For 99.2% of the global adult population, individual salt (NaCl) intake exceeds the maximum limit recommended by the World Health Organization[1,2]. The development of single-cell RNA sequencing (scRNA-seq) has made it possible to systematically study heterogeneity across a large number of individual cells in normal and diseased tissue[14,15]. The cell composition and heterogeneity of murine and human aortae in different diseases have been described using unbiased scRNA-seq[16,17,18,19]. These studies characterized the extensive transcriptional and functional heterogeneity of vascular cells during the progression of diseases
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
