Alice Wang1, Lydia Coulter Kwee2, Elizabeth Grass2, Megan L Neely1, Simon G Gregory2, Keith A A Fox3, Paul W Armstrong4, Harvey D White5, E Magnus Ohman6, Matthew T Roe1, Svati H Shah7, Mark Y Chan8. 1. Duke Clinical Research Institute, Durham, NC, United States. 2. Duke Molecular Physiology Institute, Durham, NC, United States. 3. St. Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, United Kingdom. 4. Canadian VIGOUR Centre and Division of Cardiology, Department of Medicine, University of Alberta, Edmonton, Alberta, Canada. 5. Green Lane Cardiovascular Service, Auckland City Hospital, Auckland, New Zealand. 6. Department of Cardiovascular Medicine, Duke University Medical Center, Durham, NC, United States. 7. Duke Molecular Physiology Institute, Durham, NC, United States. Electronic address: svati.shah@dm.duke.edu. 8. Division of Cardiology, Department of Medicine, National University of Singapore, Singapore. Electronic address: mark_chan@nuhs.edu.sg.
Abstract
BACKGROUND AND AIMS: Although circulating microRNA (miRNAs) have emerged as biomarkers predicting mortality in acute coronary syndrome (ACS), more data are needed to understand these mechanisms. Mapping miRNAs to high-risk traits may identify miRNAs involved in pathways conferring risk for poor outcome in ACS. We aim to investigate the relationship between circulating miRNAs and high-risk traits in non-ST-segment elevation acute coronary syndrome (NSTE-ACS). METHODS:Whole-genome miRNA sequencing was performed on RNA extracted from whole blood of 199 patients with NSTE-ACS. Generalized linear models were used to test associations of miRNAs and 13 high-risk clinical traits, including the Global Registry of Acute Coronary Events (GRACE) score, a widely validated risk score for mortality in NSTE-ACS. RESULTS: There were 205 nominally significant miRNA-risk factor associations (p < 0.05) observed. Significant associations occurred most frequently with chronic heart failure (HF) (43 miRs), GRACE risk score (30 miRs), and renal function (32 miRs). In hierarchical cluster analysis, chronic HF and GRACE risk score clustered most tightly together, sharing 14 miRNAs with matching fold-change direction. Controlling for a false discovery rate of 5%, chronic HF was significantly associated with lower circulating levels of miR-3135b (p < 0.0006), miR-126-5p (p < 0.0001), miR-142-5p (p = 0.0004) and miR-144-5p (p = 0.0007), while increasing GRACE risk score inversely correlated with levels of miR-3135b (p < 0.0001) and positively correlated with levels of miR-28-3p (p = 0.0002). CONCLUSIONS: Circulating miRs clustered around two powerful traits for mortality risk in NSTE-ACS. MiR-3135b, which was under-expressed in chronic HF and increasing GRACE risk score, and miR-28-3p, which has no known association with cardiovascular disease, warrant further investigation.
RCT Entities:
BACKGROUND AND AIMS: Although circulating microRNA (miRNAs) have emerged as biomarkers predicting mortality in acute coronary syndrome (ACS), more data are needed to understand these mechanisms. Mapping miRNAs to high-risk traits may identify miRNAs involved in pathways conferring risk for poor outcome in ACS. We aim to investigate the relationship between circulating miRNAs and high-risk traits in non-ST-segment elevation acute coronary syndrome (NSTE-ACS). METHODS: Whole-genome miRNA sequencing was performed on RNA extracted from whole blood of 199 patients with NSTE-ACS. Generalized linear models were used to test associations of miRNAs and 13 high-risk clinical traits, including the Global Registry of Acute Coronary Events (GRACE) score, a widely validated risk score for mortality in NSTE-ACS. RESULTS: There were 205 nominally significant miRNA-risk factor associations (p < 0.05) observed. Significant associations occurred most frequently with chronic heart failure (HF) (43 miRs), GRACE risk score (30 miRs), and renal function (32 miRs). In hierarchical cluster analysis, chronic HF and GRACE risk score clustered most tightly together, sharing 14 miRNAs with matching fold-change direction. Controlling for a false discovery rate of 5%, chronic HF was significantly associated with lower circulating levels of miR-3135b (p < 0.0006), miR-126-5p (p < 0.0001), miR-142-5p (p = 0.0004) and miR-144-5p (p = 0.0007), while increasing GRACE risk score inversely correlated with levels of miR-3135b (p < 0.0001) and positively correlated with levels of miR-28-3p (p = 0.0002). CONCLUSIONS: Circulating miRs clustered around two powerful traits for mortality risk in NSTE-ACS. MiR-3135b, which was under-expressed in chronic HF and increasing GRACE risk score, and miR-28-3p, which has no known association with cardiovascular disease, warrant further investigation.
Authors: Ana Mompeón; Daniel Pérez-Cremades; Ana Belén Paes; Juan Sanchis; Luis Ortega-Paz; Rut Andrea; Salvatore Brugaletta; Manel Sabate; Susana Novella; Ana Paula Dantas; Carlos Hermenegildo Journal: Cells Date: 2022-06-02 Impact factor: 7.666
Authors: Malte Kölling; Harald Seeger; George Haddad; Andreas Kistler; Albina Nowak; Robert Faulhaber-Walter; Jan Kielstein; Hermann Haller; Danilo Fliser; Thomas Mueller; Rudolf P Wüthrich; Johan M Lorenzen Journal: Kidney Int Rep Date: 2018-06-02
Authors: Kristian C Becker; Lydia Coulter Kwee; Megan L Neely; Elizabeth Grass; Joseph A Jakubowski; Keith A A Fox; Harvey D White; Simon G Gregory; Paul A Gurbel; Leonardo de Pinto Carvalho; Richard C Becker; E Magnus Ohman; Matthew T Roe; Svati H Shah; Mark Y Chan Journal: Sci Rep Date: 2020-04-10 Impact factor: 4.379