T-cell derived Extracellular Vesicles are elevated in essential HTN.

Extracellular vesicles (EVs) are novel mediators of cell-to-cell communication and appear to mediate the pathogenesis of hypertension (HTN). However, the mechanisms underlying the involvement of EVs in HTN remain unclear. The adaptive and innate immune systems (IS) play an important role affecting the kidney and vasculature in animal models of HTN. Evolving evidence shows that immune cell-derived EVs can modulate the IS in a paracrine fashion and therefore may mediate the effects of inflammation in the pathogenesis of HTN. Therefore, we aimed to understand if specific subtypes of leukocyte/immune-cell-derived EVs are altered in essential HTN using an in-vivo model of Angiotensin-II induced HTN. After 4 weeks of Ang II treatment, EVs were isolated from blood and kidney. EV's origin and counts were characterized with using flow cytometry, antibody panels targeting platelets, endothelial cells, and leukocytes including B- and T-cells, monocytes, and neutrophils. Leukocyte (CD45+) EVs were elevated in the circulation and kidney tissue in Ang-II HTN. Subgroup analysis depicted T-cell derived EVs (CD3+) to be significantly elevated in Ang-II induced HTN (3.50E+05 particles/ml) compared to control groups (9.16E+04 particles/ml, p=0.0106). T-cell derived EVs also significantly correlated with systolic blood pressure (BP) levels (r2= 0.898; p=0.0012). In summary, leukocyte-derived EVs and more specifically T-cell-derived EVs (CD3+) are elevated in Ang-II induced HTN in the circulation and kidney tissue and correlate well with BP severity. EVs from the circulation and kidney may be sensitive biomarkers for HTN and end-organ damage and may lead to new mechanistic insights in this silent disease.