Circulating microRNAs May Serve as Biomarkers for Hypertensive Emergency End-Organ Injuries and Address Underlying Pathways in an Animal Model.

Autor:	Langlo KAR; Department of Circulation and Medical Imaging, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, Norway.; Department of Nephrology, Clinic of Medicine, St. Olav's Hospital, Trondheim University Hospital, Trondheim, Norway., Silva GJJ; Department of Circulation and Medical Imaging, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, Norway.; Institute for Experimental Medical Research, Oslo University Hospital and University of Oslo, Oslo, Norway., Overrein TS; Division of Pathology and Medical Genetics, Department of Laboratory Medicine, St. Olav's Hospital, Trondheim University Hospital, Trondheim, Norway., Adams V; Department of Cardiology, Heart Center Dresden, TU Dresden, Dresden, Germany., Wisløff U; Department of Circulation and Medical Imaging, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, Norway.; School of Human Movement & Nutrition Sciences, University of Queensland, Brisbane, QLD, Australia., Dalen H; Department of Circulation and Medical Imaging, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, Norway.; Clinic of Cardiology, St. Olav's Hospital, Trondheim University Hospital, Trondheim, Norway.; Department of Medicine, Levanger Hospital, Nord-Trøndelag Hospital Trust, Levanger, Norway., Rolim N; Department of Circulation and Medical Imaging, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, Norway., Hallan SI; Department of Nephrology, Clinic of Medicine, St. Olav's Hospital, Trondheim University Hospital, Trondheim, Norway.; Department of Clinical and Molecular Medicine, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, Norway.
Jazyk:	angličtina
Zdroj:	Frontiers in cardiovascular medicine [Front Cardiovasc Med] 2021 Feb 12; Vol. 7, pp. 626699. Date of Electronic Publication: 2021 Feb 12 (Print Publication: 2020).
DOI:	10.3389/fcvm.2020.626699
Abstrakt:	There is an incomplete understanding of the underlying pathophysiology in hypertensive emergencies, where severely elevated blood pressure causes acute end-organ injuries, as opposed to the long-term manifestations of chronic hypertension. Furthermore, current biomarkers are unable to detect early end-organ injuries like hypertensive encephalopathy and renal thrombotic microangiopathy. We hypothesized that circulating microRNAs (c-miRs) could identify acute and chronic complications of severe hypertension, and that combinations of c-miRs could elucidate important pathways involved. We studied the diagnostic accuracy of 145 c-miRs in Dahl salt-sensitive rats fed either a low-salt ( N = 20: 0.3% NaCl) or a high-salt ( N = 60: 8% NaCl) diet. Subclinical hypertensive encephalopathy and thrombotic microangiopathy were diagnosed by histopathology. In addition, heart failure with preserved ejection fraction was evaluated with echocardiography and N-terminal pro-brain natriuretic peptide; and endothelial dysfunction was studied using acetylcholine-induced aorta ring relaxation. Systolic blood pressure increased severely in animals on a high-salt diet (high-salt 205 ± 20 mm Hg vs. low-salt 152 ± 18 mm Hg, p < 0.001). Partial least squares discriminant analysis revealed 68 c-miRs discriminating between animals with and without hypertensive emergency complications. Twenty-nine c-miRs were strongly associated with hypertensive encephalopathy, 24 c-miRs with thrombotic microangiopathy, 30 c-miRs with heart failure with preserved ejection fraction, and 28 c-miRs with endothelial dysfunction. Hypertensive encephalopathy, thrombotic microangiopathy and heart failure with preserved ejection fraction were associated with deviations in many of the same c-miRs, whereas endothelial dysfunction was associated with a different set of c-miRs. Several of these c-miRs demonstrated fair to good diagnostic accuracy for a composite outcome of hypertensive encephalopathy, thrombotic microangiopathy and heart failure with preserved ejection fraction in receiver-operating-curve analyses (area-under-curve 0.75-0.88). Target prediction revealed an enrichment of genes related to several pathways relevant for cardiovascular disease (e.g., mucin type O-glycan biosynthesis, MAPK, Wnt, Hippo, and TGF-beta signaling). C-miRs could potentially serve as biomarkers of severe hypertensive end-organ injuries and elucidate important pathways involved. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2021 Langlo, Silva, Overrein, Adams, Wisløff, Dalen, Rolim and Hallan.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu