Extracellular Vesicles in Essential Hypertension: Hidden Messengers

Hypertension affects about half of all Americans, yet in the vast majority of cases, the factors causing the hypertension cannot be clearly delineated. Developing a more precise understanding of the molecular pathogenesis of HTN and its various phenotypes is therefore a pressing priority. Circulating and urinary extracellular vesicles (EVs) are potential novel candidates as biomarkers and bioactivators in HTN. EVs are a heterogeneous population of small membrane fragments shed from various cell types into various body fluids. As EVs carry protein, RNA, and lipids, they also play a role as effectors and novel cell-to-cell communicators. In this review, we discuss the diagnostic, functional, and regenerative role of EVs in essential HTN and focus on EV protein and RNA cargo as the most extensively studied EV cargo.

The field of EVs in HTN is still a young one and earlier studies have not used the novel EV detection tools currently available. More rigor and transparency in EV research are needed. Current data suggest that EVs represent potential novel biomarkers in HTN. EVs correlate with HTN severity and possibly end-organ damage. However, it has yet to be discerned which specific subtype(s) of EV reflects best HTN pathophysiology. Evolving studies are also showing that EVs might be novel regulators in vascular and renal tubular function and also be therapeutic. RNA in EVs has been studied in the context of hypertension, largely in the form of studies of miRNA, which are reviewed herein. Beyond miRNAs, mRNA in urinary EVs changed in response to sodium loading in humans. EVs represent promising novel biomarkers and bioactivators in essential HTN. Novel tools are being developed to apply more rigor in EV research including more in vivo models and translation to humans.