{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T14:48:30Z","timestamp":1779893310797,"version":"3.53.1"},"reference-count":50,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2021,4,14]],"date-time":"2021-04-14T00:00:00Z","timestamp":1618358400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diagnostics"],"abstract":"<jats:p>Background: Although cardiovascular imaging techniques are widely used to diagnose myocardial ischemia in patients with suspected stable coronary artery disease (CAD), they have limitations related to lack of specificity, sensitivity and \u201clate\u201d diagnosis. Additionally, the absence of a simple laboratory test that can detect myocardial ischemia in CAD patients, has led to many patients being first diagnosed at the time of the development of myocardial infarction. Nourin is an early blood-based biomarker rapidly released within five minutes by \u201creversible\u201d ischemic myocardium before progressing to necrosis. Recently, we demonstrated that the Nourin-dependent miR-137 (marker of cell damage) and miR-106b-5p (marker of inflammation) can diagnose myocardial ischemia in patients with unstable angina (UA) and also stratify severity of ischemia, with higher expression in acute ST-segment elevation myocardial infarction (STEMI) patients compared to UA patients. Minimal baseline-gene expression levels of Nourin miRNAs were detected in healthy subjects. Objectives: To determine: (1) whether Nourin miRNAs are elevated in chest pain patients with myocardial ischemia suspected of CAD, who also underwent dobutamine stress echocardiography (DSE) or ECG\/Treadmill stress test, and (2) whether the elevated levels of serum Nourin miRNAs correlate with results of ECHO\/ECG stress test in diagnosing CAD patients. Methods: Serum gene expression levels of miR-137, miR-106b-5p and their corresponding molecular pathway network were measured blindly in 70 enrolled subjects using quantitative real time PCR (qPCR). Blood samples were collected from: (1) patients with chest pain suspected of myocardial ischemia (n = 38) both immediately \u201cpre-stress test\u201d and \u201cpost-stress test\u201d 30 min. after test termination; (2) patients with acute STEMI (n = 16) functioned as our positive control; and (3) healthy volunteers (n = 16) who, also, exercised on ECG\/Treadmill stress test for Nourin baseline-gene expression levels. Results: (1) strong correlation was observed between Nourin miRNAs serum expression levels and results obtained from ECHO\/ECG stress test in diagnosing myocardial ischemia in CAD patients; (2) positive \u201cpost-stress test\u201d patients with CAD diagnosis showed upregulation of miR-137 by 572-fold and miR-106b-5p by 122-fold, when compared to negative \u201cpost-stress test\u201d patients (p &lt; 0.001); (3) similarly, positive \u201cpre-stress test\u201d CAD patients showed upregulation of miR-137 by 1198-fold and miR-106b-5p by 114-fold, when compared to negative \u201cpre-stress test\u201d patients (p &lt; 0.001); and (4) healthy subjects had minimal baseline-gene expressions of Nourin miRNAs. Conclusions: Nourin-dependent miR-137 and miR-106b-5p are promising novel blood-based biomarkers for early diagnosis of myocardial ischemia in chest pain patients suspected of CAD in outpatient clinics. Early identification of CAD patients, while patients are in the stable state before progressing to infarction, is key to providing crucial diagnostic steps and therapy to limit adverse cardiac events, improve patients\u2019 health outcome and save lives.<\/jats:p>","DOI":"10.3390\/diagnostics11040703","type":"journal-article","created":{"date-parts":[[2021,4,14]],"date-time":"2021-04-14T15:30:39Z","timestamp":1618414239000},"page":"703","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Nourin-Dependent miR-137 and miR-106b: Novel Biomarkers for Early Diagnosis of Myocardial Ischemia in Coronary Artery Disease Patients"],"prefix":"10.3390","volume":"11","author":[{"given":"Salwa A.","family":"Elgebaly","sequence":"first","affiliation":[{"name":"Research &amp; Development, Nour Heart, Inc., Vienna, VA 22180, USA"},{"name":"Department of Surgery, UConn Health, School of Medicine, Farmington, CT 06032, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert H.","family":"Christenson","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Maryland School of Medicine, Baltimore, MD 21201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hossam","family":"Kandil","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Kasr Alainy Faculty of Medicine, Cairo University, Cairo 11562, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohsen","family":"Ibrahim","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Kasr Alainy Faculty of Medicine, Cairo University, Cairo 11562, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hussien","family":"Rizk","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Kasr Alainy Faculty of Medicine, Cairo University, Cairo 11562, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6646-4674","authenticated-orcid":false,"given":"Nashwa","family":"El-Khazragy","sequence":"additional","affiliation":[{"name":"Department of Clinical Pathology-Hematology, Ain Shams Medical Research Institute (MASRI), Faculty of Medicine, Ain Shams University, Cairo 11566, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laila","family":"Rashed","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Kasr Alainy Faculty of Medicine, Cairo University, Cairo 11562, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5818-1770","authenticated-orcid":false,"given":"Beshoy","family":"Yacoub","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Kasr Alainy Faculty of Medicine, Cairo University, Cairo 11562, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heba","family":"Eldeeb","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Kasr Alainy Faculty of Medicine, Cairo University, Cairo 11562, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mahmoud M.","family":"Ali","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Kasr Alainy Faculty of Medicine, Cairo University, Cairo 11562, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donald L.","family":"Kreutzer","sequence":"additional","affiliation":[{"name":"Department of Surgery, UConn Health, School of Medicine, Farmington, CT 06032, USA"},{"name":"Cell &amp; Molecular Tissue Engineering, LLC, Farmington, CT 06032, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,4,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"256","DOI":"10.21037\/atm.2016.06.33","article-title":"Epidemiology of coronary heart disease and acute coronary syndrome","volume":"4","author":"Leischik","year":"2016","journal-title":"Ann. 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Outcomes"}],"container-title":["Diagnostics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-4418\/11\/4\/703\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T05:48:01Z","timestamp":1760161681000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-4418\/11\/4\/703"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,4,14]]},"references-count":50,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2021,4]]}},"alternative-id":["diagnostics11040703"],"URL":"https:\/\/doi.org\/10.3390\/diagnostics11040703","relation":{},"ISSN":["2075-4418"],"issn-type":[{"value":"2075-4418","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,4,14]]}}}