Regulation of human salt-sensitivite hypertension by myeloid cell renin-angiotensin-aldosterone system

Figures

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  FIGURE 1. (A) Experimental design for bulk RNA sequencing. Human monocytes from 11 healthy subjects were isolated and cultured in either high salt (190 mmol/L NaCl) or normal salt (150 mmol/L NaCl) for 72 h (B), Expression differences in RAS-related genes in response to normal salt and high salt treatment are presented in reads per kilobase per million mapped reads (RPKM). (C) A heatmap of RNA transcripts illustrating RAS-related gene expression differences in response to normal salt and high salt treatment is provided. Bright pink, bright blue, and white represent the highest, lowest, and median read values, respectively. Rows represent individual genes and columns represent individual samples. Panel A created with BioRender.com.

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  FIGURE 2. (A) The experimental design showing the inpatient protocol of salt loading (day 1) and salt depletion (day 2). (B) Experimental setup of the human peripheral blood mononuclear cells CITE-Sequence Analysis. Panel B created with BioRender.com.

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  FIGURE 3. (A) UMAP representation of immune cell type clusters identified by antibody-derived tags. (B) Gene expression of Angiotensin II Receptor Associated Protein (AGTRAP), Renin Binding Protein (RENBP), Renin (REN), MAS1 proto-oncogene (MAS1) which encodes angiotensin-(1-7) receptor, Nuclear receptor subfamily 3 group c member 2 (NR3C2) which encodes the mineralocorticoid receptor, ATPase H+ transporting accessory protein 2 (ATP6AP2) which encodes the (pro)renin receptor, angiotensin I converting enzyme (ACE), angiotensin I converting enzyme 2 (ACE2), Chloride transport protein 6 (CLCN6), and Natriuretic Peptide A (NPPA) in different cell clusters are presented in UMAPs. (C) Dot plot of RAAS-related gene expressions in different cell clusters.

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  FIGURE 4. UMAP representation of gene expression of AGTRAP, ATP6AP2, RENBP, ACE, CLCN6, and NR3C2 are shown at baseline (B), salt loading (SL) and salt depletion (SD) in select salt resistant and salt sensitive subjects.

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  FIGURE 5. (A) Mean ± SEM of systolic blood pressures (SBP). (B) Mean ± SEM of the change in SBP from baseline (B) to salt loading (SL), and from salt loading to salt depletion (SD). *p < 0.05 assessed by Wilcoxon rank-sum test. (C) Mean ± SEM of plasma renin concentration, plasma aldosterone, and aldosterone/renin ratio (ARR) atB, SLand SD. The red, blue and black lines represent the patients with the highest, the lowest and intermediate salt sensitivity index, respectively.

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  FIGURE 6. The correlations of baseline renin, aldosterone, ARR and changes (∆) in renin, aldosterone and ARR from salt loading to salt depletion (SL-SD) with salt sensitivity index. Three patients with the highest salt sensitivity index were represented as salt sensitive (red); three patients with intermediate salt sensitivity index were represented as intermediate (black); three patients with the lowest salt sensitivity index were represented as salt resistant (blue).