Hypertension is a leading risk factor for global burden of disease. End-organ damage to the kidneys, heart, brain, and vasculature is an important manifestation of this disease. As such, those who suffer from hypertension are more likely to develop atherosclerosis, stroke, myocardial infarction, heart failure, chronic kidney disease, and dementia. Yet, in the majority of adults with hypertension, the cause is not completely understood. It is thought that the innate and adaptive immune systems play an essential role in hypertension by affecting the vasculature and kidney. Emerging evidence supports an important role for T cells in the genesis of hypertension. However, there is a poor understanding of how these immune cells interact and the mediation of their actions in the vasculature and target organs like the kidney to affect blood pressure. Extracellular vesicles are potential new biomarkers, bioactivators and communicators that have been found to play a major role in regulating the immune system. Few studies have been done on the immune regulatory role of extracellular vesicles in essential hypertension. However, it appears that they may influence the pathogenesis of hypertension, but the mechanisms underlying this involvement are unclear.
In a new study published in the American Journal of Physiology-Renal Physiology, University of Virginia scientists: Sabrina La Salvia, Luca Musante and Joanne Lannigan and led by Professor Uta Erdbrügger investigated the involvement of extracellular vesicles in essential hypertension and if specific subtypes of leukocyte/ immune cell-derived extracellular vesicles are affected in essential hypertension. The research team findings showed that there is an increase in T cell-derived extracellular vesicles (CD3+) in the circulation and kidney tissue in an angiotensin II-induced hypertension model and this correlates with blood pressure severity. Dr. Joseph Gigliotti at Liberty University College of Osteopathic Medicine and Professor Thu H. Le at University of Rochester Medical Center contributed also to the study.
In their experiments, while the authors observed no differences in the sizes and number of extracellular vesicles from both hypertensive and normotensive mice. However, compared to normotensive mice, higher counts of leukocyte-derived extracellular vesicles (CD45+) were found in the kidneys of hypertensive animals. These kidney-isolated extracellular vesicles also correlated with severity in systolic blood pressure level.
Blood pressure lowering was noticed to have an influence on the levels of extracellular vesicles. Specifically, there was numerical lowering of leukocyte-derived extracellular vesicles (CD45+) following treatment with various blood pressure lowering drug regimens compared to the control group.
A further analysis of different subgroups of leukocyte-derived extracellular vesicles showed that T cell-derived extracellular vesicles (CD3+) were elevated in angiotensin II-induced hypertension. In mice treated with different blood pressure lowering drug regimens, a numerical reduction in T cell-derived extracellular vesicles (CD3+) was observed. In contrast, no differences were seen in the levels of neutrophil (Ly6g+/CD11b)-, B cell (CD19+)-, and monocyte (Ly6g/CD11b+) derived extracellular vesicles.
In summary, Professor Uta Erdbrügger and colleagues have been able to demonstrate that in hypertension, extracellular vesicles likely regulate immune processes and are potential messengers in the kidneys and vasculature. Thus extracellular vesicles might play an important role in the pathogenesis of hypertension in addition to serving as a biomarker that indicates the severity of hypertension. The authors recommended in the future studies be carried out to analyze and investigate the functional role of subtypes of circulating extracellular vesicles. Furthering our understanding of the new discovered extracellular vesicles contributing to hypertension can potentially lead to the development of new and more effective therapies.
La Salvia S, Musante L, Lannigan J, Gigliotti JC, Le TH, Erdbrügger U. T cell-derived extracellular vesicles are elevated in essential HTN. Am J Physiol Renal Physiol. 2020 ;319(5):F868-F875.Go To Am J Physiol Renal Physiol