T cell-derived extracellular vesicles are elevated in essential HTN

Abstract

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.

Extracellular Vesicles as Drivers of Immunoinflammation in Atherothrombosis

“…In this context, EVs emerge as promising biomarkers for CV risk stratification. We found that patients with familial hypercholesterolemia (FH) presenting subclinical lipid-rich atherosclerotic plaques have significantly higher amounts of circulating lymphocyte-derived (CD3 + /CD45 + ) EVs than FH patients with fibrous plaques [ 50 ] in agreement with other studies that reported high levels of EVs from T lymphocytes in subjects with essential hypertension [ 235 ] and about to develop a MACE [ 265 ]. Thus, lymphocyte-derived EVs might help to map atherosclerotic plaque burden.…”

“…Molecular footprints of EVs provide clues about their cellular origin under healthy and diseased states, configuring a precious biomedical tool for liquid biopsy, easily detectable in body fluids. Changes in circulating EVs of different cellular origin have been widely reported for almost all cardiovascular risk factors [ 233 , 234 , 235 , 236 ] and pathologies [ 237 , 238 , 239 ] reflecting their pathophysiological severity. Beyond diagnostic use, EVs have been suggested for the prediction of major adverse cardiovascular events (MACE) [ 230 , 231 , 232 , 233 , 234 , 235 , 236 , 237 , 238 , 239 , 240 , 241 , 242 , 243 ] and mortality [ 244 ].…”

“…Changes in circulating EVs of different cellular origin have been widely reported for almost all cardiovascular risk factors [ 233 , 234 , 235 , 236 ] and pathologies [ 237 , 238 , 239 ] reflecting their pathophysiological severity. Beyond diagnostic use, EVs have been suggested for the prediction of major adverse cardiovascular events (MACE) [ 230 , 231 , 232 , 233 , 234 , 235 , 236 , 237 , 238 , 239 , 240 , 241 , 242 , 243 ] and mortality [ 244 ]. Circulating procoagulant MVs were found at higher levels in patients with ACS than healthy subjects [ 238 , 239 , 240 , 245 , 246 , 247 , 248 , 249 , 250 , 251 , 252 , 253 , 254 , 255 ].…”

Urinary Extracellular Vesicles Are a Novel Tool to Monitor Allograft Function in Kidney Transplantation: A Systematic Review

“…CD3+ uEV show strong positive correlations with kidney allograft rejection [ 23 ]. However, in renal tissue, CD3+ EVs and CD45+ EVs are also significantly elevated in hypertension-related kidney injury [ 55 ]. Moreover, CD3+ T cells markedly infiltrate renal tubules and interstitium during DN, leading to chronic inflammation [ 56 ].…”

Role and Function of T Cell-Derived Exosomes and Their Therapeutic Value

“…In an angiotensin-induced HTN animal model, CD3+ T cellderived exosomes entered peripheral circulation and the kidneys. They also found that the concentration of exosomes was positively correlated with high blood pressure [33].…”