title: Signatures of miR-181a on the Renal Transcriptome and Blood Pressure.
abstract: MicroRNA-181a binds to the 3' untranslated region of messenger RNA (mRNA) for renin, a rate-limiting enzyme of the renin-angiotensin system. Our objective was to determine whether this molecular interaction translates into a clinically meaningful effect on blood pressure and whether circulating miR-181a is a measurable proxy of blood pressure. In 200 human kidneys from the TRANScriptome of renaL humAn TissuE (TRANSLATE) study, renal miR-181a was the sole negative predictor of renin mRNA and a strong correlate of circulating miR-181a. Elevated miR-181a levels correlated positively with systolic and diastolic blood pressure in TRANSLATE, and this association was independent of circulating renin. The association between serum miR-181a and systolic blood pressure was replicated in 199 subjects from the Genetic Regulation of Arterial Pressure of Humans In the Community (GRAPHIC) study. Renal immunohistochemistry andin situhybridization showed that colocalization of miR-181a and renin was most prominent in collecting ducts where renin is not released into the systemic circulation. Analysis of 69 human kidneys characterized by RNA sequencing revealed that miR-181a was associated with downregulation of four mitochondrial pathways and upregulation of 41 signaling cascades of adaptive immunity and inflammation. We conclude that renal miR-181a has pleiotropic effects on pathways relevant to blood pressure regulation and that circulating levels of miR-181a are both a measurable proxy of renal miR-181a expression and a novel biochemical correlate of blood pressure.
authors: Faculty of Science and Technology, School of Applied and Biomedical Sciences, Federation University Australia, Victoria, Australia.
authors: Francine Z
authors: FZ
authors: Marques
authors: Department of Cardiovascular Sciences, University of Leicester, Leicester, United Kingdom.
authors: Simon Pr
authors: SP
authors: Romaine
authors: Department of Cardiovascular Sciences, University of Leicester, Leicester, United Kingdom.
authors: Matthew
authors: M
authors: Denniff
authors: Department of Cardiovascular Sciences, University of Leicester, Leicester, United Kingdom.
authors: James
authors: J
authors: Eales
authors: University Hospitals of Leicester NHS Trust, Leicester, United Kingdom.
authors: John
authors: J
authors: Dormer
authors: Division of Pharmacology and Vascular Medicine, Department of Internal Medicine, Erasmus Medical Centre, Rotterdam, The Netherlands.
authors: Ingrid M
authors: IM
authors: Garrelds
authors: Department of Urology and Oncological Urology, Poznan University of Medical Sciences, Poznan, Poland.
authors: Lukasz
authors: L
authors: Wojnar
authors: Department of Education and Obesity Treatment and Metabolic Disorders, Poznan University of Medical Sciences, Poznan, Poland.
authors: Katarzyna
authors: K
authors: Musialik
authors: Department of Internal Medicine, Diabetology and Nephrology, Medical University of Silesia, Zabrze, Poland.
authors: Barbara
authors: B
authors: Duda-Raszewska
authors: Department of Internal Medicine, Diabetology and Nephrology, Medical University of Silesia, Zabrze, Poland.
authors: Bartlomiej
authors: B
authors: Kiszka
authors: Department of Internal Medicine, Diabetology and Nephrology, Medical University of Silesia, Zabrze, Poland.
authors: Magdalena
authors: M
authors: Duda
authors: School of Medical Sciences, University of Sydney, New South Wales, Australia.
authors: Brian J
authors: BJ
authors: Morris
authors: Department of Cardiovascular Sciences, University of Leicester, Leicester, United Kingdom.|Leicester National Institute for Health Research Biomedical Research Unit in Cardiovascular Disease, Glenfield Hospital, Leicester, United Kingdom.
authors: Nilesh J
authors: NJ
authors: Samani
authors: Division of Pharmacology and Vascular Medicine, Department of Internal Medicine, Erasmus Medical Centre, Rotterdam, The Netherlands.
authors: Ah Jan
authors: AJ
authors: Danser
authors: Department of Education and Obesity Treatment and Metabolic Disorders, Poznan University of Medical Sciences, Poznan, Poland.
authors: Pawel
authors: P
authors: Bogdanski
authors: Department of Internal Medicine, Diabetology and Nephrology, Medical University of Silesia, Zabrze, Poland.
authors: Ewa
authors: E
authors: Zukowska-Szczechowska
authors: Faculty of Science and Technology, School of Applied and Biomedical Sciences, Federation University Australia, Victoria, Australia.
authors: Fadi J
authors: FJ
authors: Charchar
authors: Department of Cardiovascular Sciences, University of Leicester, Leicester, United Kingdom.|Institute of Cardiovascular Sciences, University of Manchester, Manchester, United Kingdom.
authors: Maciej
authors: M
authors: Tomaszewski