Essential hypertension is one of the major modifiable risk factors contributing to the clinical manifestations of cardiovascular, cerebrovascular and renal diseases. The complexity of the disease is attributed to genetic, epigenetic and environmental components [1]. The prevalence of high blood pressure has recently shifted from high-middle-income countries to low-middle-income countries. This drift may be largely attributed to age, gender, lifestyle factors, race and ethnicity, and prevailing comorbid conditions in the population studied [2]. Despite the intense knowledge accumulated over the past several decades on the physiological pathways and genes associated with EH, several lacunae remain in hypertension genetics, which have to be resolved to identify the genetic hub related to this phenotype. Prompt diagnosis and early medical intervention would aid in minimizing the complications due to increased blood pressure. In an attempt to identify novel theragnostic (therapeutic and diagnostic) markers for EH, we turned our focus towards exosomes, which are extracellular vesicles derived from various cell types. Exosomes are found in almost all body fluids, such as saliva, breast milk, cerebrospinal fluid, and urine, and are thus a noninvasive source of biomarkers. These microvesicular bodies contain enormous information in the form of proteins and RNAs such as mRNAs, microRNAs (miRNAs) and other noncoding RNAs [3]. miRNAs are chromosomally encoded, small noncoding RNAs that can potentially influence the posttranscriptional process of target gene expression by regulating the translation of mRNA and maintenance of its stability in the cytoplasm. In addition, numerous studies have documented that miRNAs are associated with different forms of hypertension, including pulmonary hypertension. A recent report documents the emerging role of miRNAs in arterial fibrillation (AF) by reviewing the polymorphisms in miRNAs and correlating the observed variations with AF. As miRNAs play a significant role in heart development, any dysregulation in miRNA expression is linked to cardiac remodeling [4].

Consistent with this observation, the present study was designed to identify exosomal miRNAs in EH patients using computational tools. A recent study conducted by Ye et al. formed the basis for this research approach. The results of the study were quite promising and identified ~257 differentially expressed miRNAs in EH patients compared to control groups in the Uyghur population. These results were based on microarray data, which were further validated using quantitative real-time quantitative PCR (qRT-PCR). Among the 257 identified miRNAs, 47 were found to have target genes [5]. In the present study, each of these miRNAs was further queried against a list of 1424 miRNAs of different genera available in the ExoCarta database, including Homo sapiens [6]. Nearly 20 miRNAs from each group of upregulated and downregulated miRNAs were found to be located in the exosomes (Table 1). Although most of these exosomal miRNAs were associated with colorectal cancer cells, a few of the miRNAs were found to be derived from other sources, such as plasma, serum, B cells, T cells and dendritic cells.

Table 1 List of microRNAs upregulated and downregulated during EH found in the exosomes as analysed using ExoCarta
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Supporting evidence from the text mining process identified miR-575 as an influencing factor in the process of angiogenesis. Zhao et al. demonstrated the upregulation of miR-575 in essential hypertensive patients with increased carotid intima-media thickness (CIMT), which is a marker of atherosclerosis, compared to patients with low CIMT [7]. A similar study of hypertension in animal models to evaluate the association of gestational protein restriction with low birth weight revealed that miR-484 is downregulated in the gestational protein-restricted left ventricle of Wistar rats compared to normal controls [8]. A prediction model constructed for salt-sensitive hypertension recognized miR-361-5p as a preferable marker, as interpreted via high-throughput miRNA sequencing and qRT-PCR [9]. Solayman et al. used the “endogenous control method” to identify normalizers that are expressed endogenously via a relative quantification approach. These normalizers produce stable expression in varying disease conditions along with experimental variables. The analysis revealed that miR-92a-3p was the best normalizer for qRT-PCR data, as it was differentially expressed between hypertensive patients and healthy controls. The level of expression of this marker was found to be consistent in both plasma and urine samples [10]. Henceforth, in vitro experiments using a larger sample size pooled from different geographical locations worldwide are warranted to elucidate the presence, location and differential expression of miRNAs linked to EH. The results of such retrospective studies could enable the identification of crucial miRNA biomarkers that can be used as promising diagnostic as well as therapeutic tools for essential hypertension.