{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T09:47:16Z","timestamp":1789984036582,"version":"4.0.1"},"reference-count":64,"publisher":"American Physiological Society","issue":"10","funder":[{"DOI":"10.13039\/501100001349","name":"Singapore National Medical Research Council","doi-asserted-by":"crossref","award":["NMRC\/CSA-INV\/0001\/2016"],"award-info":[{"award-number":["NMRC\/CSA-INV\/0001\/2016"]}],"id":[{"id":"10.13039\/501100001349","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Physiological Genomics"],"published-print":{"date-parts":[[2019,10,1]]},"abstract":"<jats:p> The genomic regulatory networks underlying the pathogenesis of non-ST-segment elevation acute coronary syndrome (NSTE-ACS) are incompletely understood. As intermediate traits, protein biomarkers report on underlying disease severity and prognosis in NSTE-ACS. We hypothesized that integration of dense microRNA (miRNA) profiling with biomarker measurements would highlight potential regulatory pathways that underlie the relationships between prognostic biomarkers, miRNAs, and cardiovascular phenotypes. We performed miRNA sequencing using whole blood from 186 patients from the TRILOGY-ACS trial. Seven circulating prognostic biomarkers were measured: NH<jats:sub>2<\/jats:sub>-terminal pro-B-type natriuretic peptide (NT-proBNP), high-sensitivity C-reactive protein, osteopontin (OPN), myeloperoxidase, growth differentiation factor 15, monocyte chemoattractant protein, and neopterin. We tested miRNAs for association with each biomarker with generalized linear models and controlled the false discovery rate at 0.05. Ten miRNAs, including known cardiac-related miRNAs 25-3p and 423-3p, were associated with NT-proBNP levels (min. P = 7.5 \u00d7 10<jats:sup>\u22124<\/jats:sup>) and 48 miRNAs, including cardiac-related miRNAs 378a-3p, 20b-5p and 320a, -b, and -d, were associated with OPN levels (min. P = 1.6 \u00d7 10<jats:sup>\u22126<\/jats:sup>). NT-proBNP and OPN were also associated with time to cardiovascular death, myocardial infarction (MI), or stroke in the sample. By integrating large-scale miRNA profiling with circulating biomarkers as intermediate traits, we identified associations of known cardiac-related and novel miRNAs with two prognostic biomarkers and identified potential genomic networks regulating these biomarkers. These results, highlighting plausible biological pathways connecting miRNAs with biomarkers and outcomes, may inform future studies seeking to delineate genomic pathways underlying NSTE-ACS outcomes. <\/jats:p>","DOI":"10.1152\/physiolgenomics.00033.2019","type":"journal-article","created":{"date-parts":[[2019,9,18]],"date-time":"2019-09-18T07:07:45Z","timestamp":1568790465000},"page":"506-515","source":"Crossref","is-referenced-by-count":10,"title":["Associations of osteopontin and NT-proBNP with circulating miRNA levels in acute coronary syndrome"],"prefix":"10.1152","volume":"51","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6997-8571","authenticated-orcid":false,"given":"Lydia Coulter","family":"Kwee","sequence":"first","affiliation":[{"name":"Duke Molecular Physiology Institute, Durham, North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Megan L.","family":"Neely","sequence":"additional","affiliation":[{"name":"Duke Clinical Research Institute, Durham, North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth","family":"Grass","sequence":"additional","affiliation":[{"name":"Duke Molecular Physiology Institute, Durham, North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon G.","family":"Gregory","sequence":"additional","affiliation":[{"name":"Duke Molecular Physiology Institute, Durham, North Carolina"},{"name":"Department of Neurology, Duke University School of Medicine, Durham, North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew T.","family":"Roe","sequence":"additional","affiliation":[{"name":"Duke Clinical Research Institute, Durham, North Carolina"},{"name":"Division of Cardiology, Department of Medicine, Duke University School of Medicine, Durham, North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E. 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