title: 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.
authors.affiliation: School of Applied and Biomedical Sciences, Faculty of Science and Technology, Federation University Australia, Mount Helen, VIC, Australia.|Heart Failure Research Group, Baker IDI Heart and Diabetes Institute, Melbourne, VIC, Australia.
authors.forename: Francine Z
authors.initials: FZ
authors.lastname: Marques
authors.affiliation: School of Applied and Biomedical Sciences, Faculty of Science and Technology, Federation University Australia, Mount Helen, VIC, Australia. f.charchar@federation.edu.au.
authors.forename: Fadi J
authors.initials: FJ
authors.lastname: Charchar
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D000818:Animals; D001794:Blood Pressure / Q000235:genetics* / Q000502:physiology; D004195:Disease Models, Animal; D000075222:Essential Hypertension; D005786:Gene Expression Regulation; D059647:Gene-Environment Interaction; D006801:Humans; D006973:Hypertension / Q000235:genetics* / Q000503:physiopathology; D035683:MicroRNAs / Q000235:genetics*; D008957:Models, Genetic
chemical_list: D020413:3' Untranslated Regions; D035683:MicroRNAs
keywords: Arterial pressure; Biomarkers; Blood pressure; Circulating microRNAs; Endothelial cells; Essential hypertension; Kidney; Plasma