microRNAs 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 mechanisms besides coding genes are likely to contribute to BP regulation. Non-coding RNAs, especially microRNAs, 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 microRNAs associated with regulation of BP and hypertension, highlighting investigations, methodology and difficulties arising in the field. These molecules are being studied for exploitation in diagnostics, prognostics and therapeutics in many diseases. There have been some studies that examined biological fluid microRNAs as biomarkers for hypertension, but most remain inconclusive due to the small sample sizes and differences in methodological standardisation. Fewer studies have analysed tissue microRNA levels in vascular smooth muscle cells and the kidney. Others focused on the interaction between single nucleotide polymorphisms and microRNA binding sites. Studies in animals have shown that angiotensin II, high-salt diet and exercise change microRNA levels in hypertension. Treatment of spontaneously hypertensive rats with a miR-22 inhibitor and treatment of hypertensive Schlager BPH/2J mice with a miR-181a mimic decreased their BP. This supports the use of microRNAs as therapeutic targets in hypertension, and future studies should test the use of other microRNAs found in human association studies. In conclusion, there is a clear need of increased pace of human, animal and functional studies to help us understand the multifaceted roles of microRNAs as critical regulators of the development and physiology of BP.

miRNA-9 inhibits apoptosis and promotes proliferation in angiotensin II-induced human umbilical vein endothelial cells by targeting MDGA2

“…The importance of microRNAs in cardiovascular diseases is rising (Marques and Charchar, 2015). In vivo studies showed that angiotensin II induced changes in the microRNA profile during hypertension (Eskildsen et al, 2013).…”

“…The role of miRNAs in the regulation of cardiovascular diseases has attracted broad research interest (Marques and Charchar, 2015;Kontaraki et al, 2014). Racial differences of miRNA expression have also been demonstrated in the case of hypertension (Dluzen et al, 2016).…”

“…The present study utilized HUVECs as a model to demonstrate the effect of miR-9. The study provided promising results but with limitations such as the lack of tissue-specific targeting (Marques and Charchar, 2015). Due to the ubiquitous expression of miRNAs in vivo, side effects of miRNA therapy are difficult to predict.…”

“…MiRNAs have been involved in a variety of physiological and pathological processes such as cell differentiation and proliferation, inflammation, and carcinogenesis (Rupaimoole and Slack, 2017). It has been widely acknowledged that miRNAs are also associated with cardiovascular diseases (Marques and Charchar, 2015). For example, downregulation of miRNA-133 (miR-133) has been observed to lead to significant cardiac hypertrophy (Carè et al, 2007).…”

Use of Biomarkers in the Evaluation and Treatment of Hypertensive Patients

“…Transcriptomic profiles that characterise hypertension in rodent models have been established [24] and first data in human kidneys point towards differences in the expression of the gene encoding renin between hypertensive and normotensive individuals [25]. Studies into the regulation of gene expression and in particular into microRNAs are of interest in this context [26]. A recent example shows that circulating levels of miR-181a are a surrogate for renal miR-181a expression where it colocalises with renin particularly in collecting ducts and that this microRNA is differentially regulated between hypertensive and normotensive subjects [27].…”