The emerging role of non-coding RNA in essential hypertension and blood pressure regulation

Abstract

Unravelling the complete genetic predisposition to high blood pressure (BP) has proven to be challenging. This puzzle and the fact that coding regions of the genome account for less than 2% of the entire human DNA support the hypothesis that genetic mechanism besides coding genes are likely to contribute to BP regulation. Non-coding RNAs (ncRNAs) are emerging as key players of transcription regulation in both health and disease states. They control basic functions in virtually all cell types relevant to the cardiovascular system and, thus, a direct involvement with BP regulation is highly probable. Here, we review the literature about ncRNAs associated with human BP and essential hypertension, highlighting investigations, methodology and difficulties arising in the field. The most investigated ncRNAs so far are microRNAs (miRNAs), small ncRNAs that modulate gene expression by posttranscriptional mechanisms. We discuss studies that have examined miRNAs associated with BP in biological fluids, such as blood and urine, and tissues, such as vascular smooth muscle cells and the kidney. Furthermore, we review the interaction between miRNA binding sites and single nucleotide polymorphisms in genes associated with BP. In conclusion, there is a clear need for more human and functional studies to help elucidate the multifaceted roles of ncRNAs, in particular mid- and long ncRNAs in BP regulation.

Signatures of miR-181a on the Renal Transcriptome and Blood Pressure

“…Further analyses were conducted using step-wise multiple linear regression models in which clinical role of miRNAs in BP regulation has been poorly investigated, whereas their role in other complex disorders is better established (3)(4)(5).…”

“…The specific environmental factors act separately or together on major mechanisms of BP regulation (2). A growing body of evidence suggests that noncoding RNAs (ncRNAs) control a number of regulatory networks in the cardiovascular system (3)(4)(5).…”

Circulating microRNAs and hypertension—from new insights into blood pressure regulation to biomarkers of cardiovascular risk

“…Thus, microRNAs represent a complex regulatory network that controls both physiological and pathological processes fundamental to a wide variety of cardiovascular diseases, including hypertension. [5,6] In this review, we focus on circulating microRNAs as emerging biomarkers in essential hypertension, as well as their ability to provide novel insights into pathology, and to identify targets for novel therapeutic agents; studies relating to gestational hypertension and preeclampsia were not considered.…”

Noncoding RNA and epigenetic gene regulation in renal diseases

“…Detailed evaluation of these exosomes for miRNA and their mRNA targets will offer mechanistic insights into exosome biogenesis and sorting in renal pathologies. In addition to renal fibrosis in the context of DN, the role of ncRNAs in other chronic renal diseases, such as IgAN, lupus nephritis, polycystic kidney disease (PKD), hypertensive nephrosclerosis, and renal transplant nephropathy, is increasingly appreciated and detailed elsewhere [8,11,63–66]. …”

“…Kidneys are important organs that help sustain the stable composition of blood, secrete important hormones, contribute to mineral and blood pressure homeostasis and so on. Recent evidence indicates that gene regulatory mechanisms involving both protein- and nonprotein-coding players are key for homeostatic renal function as well as disease [8–11]. Here, we summarize ncRNA as well as epigenetic modifications mediating gene regulation (Fig.…”