From “a tool for removing cellular waste” to “a diagnostic tool for hypertension”, what exactly are exosomes? In fact, they are spherical extracellular vesicles of 30150 nm in diameter with a phospholipid bilayer. Let’s take a look.
1. First, what is an “exosome”?
Exosomes were originally thought to be a tool for removing cellular waste, but as research continues, they are now defined as spherical extracellular vesicles with a phospholipid bilayer of 30150 nm in diameter, and act as carriers of miRNAs (a small, siRNA-like molecule), mRNAs (messenger RNAs), proteins and lipids to play a communication and regulatory roles.
Currently, exosomes have been found in a variety of body fluids including blood, urine, saliva, breast milk and cerebrospinal fluid.
2. Which exosomes can be used to diagnose hypertension and its related diseases?
Studies in exosomes and hypertension have mainly focused on urinary-derived exosomes and found that exosomes and their contents play a regulatory role in the major pathogenic mechanisms of hypertension, such as the renin-angiotensin-aldosterone system (RAAS) and water-electrolyte balance.
(1) Role of exosomes in the renin-angiotensin-aldosterone system (RAAS)
The RAAS plays an important role in the regulation of blood pressure, and the end product angiotensin II produced by the renin-angiotensin system (RAS) not only regulates vasoconstriction, growth and fibrosis, but also increases vascular permeability by initiating an inflammatory response.
The exosomes that play a major role include those enriched in AT1R and those with reduced levels of miRNA-17 (ICAM-1 negative regulator).
It has been found that the level of phosphorylated sodium chloride co-transporter protein (pNCC) is 2.6-fold higher in urinary exosomes from patients with primary aldosteronism than in patients with primary hypertension, thus speculating that sodium chloride co-transporter protein (pNCC) in urinary exosomes is promising as a biomarker for aldosteronism.
(2) Role of exosomes in water-electrolyte homeostasis
Currently, there are more studies on urinary-derived exosomes in hypertension, and exosomes can serve as carriers of sodium transport proteins.
Related studies have shown that urinary exosomes contain sodium-hydrogen conversion pump 3 (NHE3), Na-K-2C1 co-transporter protein (NKCC-2), thiazide-sensitive sodium-chloride ion transporter protein (NCC) and epithelial sodium channel (ENaC), which play a key role in regulating blood pressure as well as electrolyte balance.
In addition, experimental studies of exosomal microRNAs (non-coding single-stranded RNA molecules of approximately 22 nucleotides in length encoded by endogenous genes) in hypertension have also progressed. These studies have significant implications for the elucidation of the pathogenesis of hypertension and the development of better prevention and treatment strategies.
MicroRNAs are endogenous small RNA molecules consisting of about 22 nucleotides that are involved in the transcriptional and post-transcriptional regulation of target genes by complementary binding to the 3’UTR of target mRNAs. Exosomes carry important miRNAs and can directly regulate gene expression through miRNAs, transmitting information to target cells where they actively promote changes in gene expression and respond to the stresses they are subjected to.
In 2013, Gilden et al. investigated miRNAs in urinary exosomes and identified 45 miRNAs that may be potential biomarkers associated with salt-sensitive hypertension. 24 of these miRNAs were identified for the first time and are thought to be specific to urinary exosomes, and these miRNAs are involved in the regulation of signaling pathways associated with AHT, reflecting the metabolic activity of the kidney, in especially the handling of sodium.
As scientific research continues to improve, there is increasing evidence that exosomes play an important role in the diagnosis of hypertensive disease and may provide biomarkers for the early diagnosis of hypertension.
The multiple biological information carried by exosomes may help to diagnose different subtypes of hypertension and enable more appropriate treatment of patients, thus further improving their quality of life.
References
[1]An Geun,Qin Lei,Hou Dongxia,Wang J,Zhou Xueyuan,Li Ling,Wang Xiaohua. Research progress of exosomes in the field of hypertension[J]. Inner Mongolia Medical Journal,2021,53(02):184-186+190.