Abstract

Hypertension is the leading risk factor for global morbidity and mortality. Emerging evidence in animal models implicates a variety of innate and adaptive immune cells in hypertension pathogenesis, and limited studies in humans have demonstrated increased circulating memory and senescent T cells in hypertensive individuals. However, the abundance and role of specific immune cells in human hypertension remains unclear. To perform unbiased high dimensional profiling of peripheral immune cells in humans, we developed and validated a novel approach using mass cytometry to detect 31 extracellular markers at the single cell level. Initial results in a normotensive individual using this panel revealed robust identification of major circulating immune cell subsets including CD4 + cells (60% of CD45 + cells), CD8 + cells (21%), γδ T cells (6%), CD25 + CD127 lo T regulatory cells (5%), CD19 + B cells (3%), and CD11c + myeloid cells (3%). Unsupervised viSNE plots using this panel of 31 markers demonstrates grouping of distinct circulating immune cell subsets based on similarity of marker levels (Figure) . We are extending this analysis to peripheral blood mononuclear cells collected from 16 additional control and 17 hypertensive individuals matched for age, gender, race, and BMI to determine differences in the abundance of known and potentially novel circulating immune cell subsets. The combination of high dimensional mapping and unsupervised computational analysis will permit rigorous immunophenotyping of human hypertension and potentially identify novel therapeutic targets.

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