PMID- 33670982 OWN - NLM STAT- MEDLINE DCOM- 20210915 LR - 20240331 IS - 2218-273X (Electronic) IS - 2218-273X (Linking) VI - 11 IP - 3 DP - 2021 Feb 28 TI - Nourin-Dependent miR-137 and miR-106b: Novel Early Inflammatory Diagnostic Biomarkers for Unstable Angina Patients. LID - 10.3390/biom11030368 [doi] LID - 368 AB - BACKGROUND: Currently, no blood biomarkers exist that can diagnose unstable angina (UA) patients. Nourin is an early inflammatory mediator rapidly released within 5 min by reversible ischemic myocardium, and if ischemia persists, it is also released by necrosis. Nourin is elevated in acute coronary syndrome (ACS) patients but not in symptomatic noncardiac and healthy subjects. Recently, circulating microRNAs (miRNAs) have been established as markers of disease, including cardiac injury and inflammation. OBJECTIVES: To profile and validate the potential diagnostic value of Nourin-dependent miR-137 (marker of cell damage) and miR-106b-5p (marker of inflammation) as early biomarkers in suspected UA patients and to investigate the association of their target and regulating genes. METHODS: Using Nourin amino acid sequence, an integrated bioinformatics analysis was conducted. Analysis indicated that Nourin is a direct target for miR-137 and miR-106b-5p in myocardial ischemic injury. Two linked molecular networks of lncRNA/miRNAs/mRNAs were also retrieved, including CTB89H12.4/miR-137/FTHL-17 and CTB89H12.4/miR-106b-5p/ANAPC11. Gene expression profiling was assessed in serum samples collected at presentation to an emergency department (ED) from: (1) UA patients (n = 30) (confirmed by invasive coronary angiography with stenosis greater than 50% and troponin level below the clinical decision limit); (2) patients with acute ST elevation myocardial infarction (STEMI) (n = 16) (confirmed by persistent ST-segment changes and elevated troponin level); and 3) healthy subjects (n = 16). RESULTS: Gene expression profiles showed that miR-137 and miR-106b-5p were significantly upregulated by 1382-fold and 192-fold in UA compared to healthy, and by 2.5-fold and 4.6-fold in STEMI compared to UA, respectively. Healthy subjects showed minimal expression profile. Receiver operator characteristics (ROC) analysis revealed that the two miRNAs were sensitive and specific biomarkers for assessment of UA and STEMI patients. Additionally, Spearman's correlation analysis revealed a significant association of miRNAs with the associated mRNA targets and the regulating lncRNA. CONCLUSIONS: Nourin-dependent gene expression of miR-137 and miR-106b-5p are novel blood-based biomarkers that can diagnose UA and STEMI patients at presentation and stratify severity of myocardial ischemia, with higher expression in STEMI compared to UA. Early diagnosis of suspected UA patients using the novel Nourin biomarkers is key for initiating guideline-based therapy that improves patients' health outcomes. FAU - Elgebaly, Salwa A AU - Elgebaly SA AD - Research & Development, Nour Heart, Inc., Vienna, VA 22180, USA. AD - Department of Surgery, UConn Health, School of Medicine, and Cell & Molecular Tissue Engineering, LLC, Farmington, CT 06032, USA. FAU - Christenson, Robert H AU - Christenson RH AD - Department of Pathology, University of Maryland, School of Medicine, Baltimore, MD 2120, USA. FAU - Kandil, Hossam AU - Kandil H AD - Department of Cardiology, Kasr Alainy Faculty of Medicine, Cairo University, Cairo 11562, Egypt. FAU - El-Khazragy, Nashwa AU - El-Khazragy N AUID- ORCID: 0000-0001-6646-4674 AD - Department of Clinical Pathology-Hematology, Ain Shams Medical Research Institute (MASRI), Faculty of Medicine, Ain Shams University, Cairo 11566, Egypt. FAU - Rashed, Laila AU - Rashed L AD - Department of Biochemistry and Molecular Biology, Kasr Alainy Faculty of Medicine, Cairo University, Cairo 11562, Egypt. FAU - Yacoub, Beshoy AU - Yacoub B AUID- ORCID: 0000-0001-5818-1770 AD - Department of Cardiology, Kasr Alainy Faculty of Medicine, Cairo University, Cairo 11562, Egypt. FAU - Eldeeb, Heba AU - Eldeeb H AD - Department of Cardiology, Kasr Alainy Faculty of Medicine, Cairo University, Cairo 11562, Egypt. FAU - Ali, Mahmoud AU - Ali M AD - Department of Cardiology, Kasr Alainy Faculty of Medicine, Cairo University, Cairo 11562, Egypt. FAU - Sharafieh, Roshanak AU - Sharafieh R AD - Department of Surgery, UConn Health, School of Medicine, and Cell & Molecular Tissue Engineering, LLC Farmington, CT 06032, USA. FAU - Klueh, Ulrike AU - Klueh U AD - Department of Biomedical Engineering, Integrative Biosciences Center (IBio), Wayne State University, Detroit, MI 48202, USA; . FAU - Kreutzer, Donald L AU - Kreutzer DL AD - Department of Surgery, UConn Health, School of Medicine, and Cell & Molecular Tissue Engineering, LLC, Farmington, CT 06032, USA. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20210228 PL - Switzerland TA - Biomolecules JT - Biomolecules JID - 101596414 RN - 0 (FTHL17 protein, human) RN - 0 (MIRN106 microRNA, human) RN - 0 (MIRN137 microRNA, human) RN - 0 (MicroRNAs) RN - 0 (RNA, Long Noncoding) RN - 0 (RNA, Messenger) RN - 9013-31-4 (Apoferritins) SB - IM MH - Acute Coronary Syndrome/genetics MH - Angina, Unstable/*diagnosis/*genetics MH - Apoferritins/genetics/metabolism MH - Case-Control Studies MH - *Early Diagnosis MH - Female MH - Humans MH - Male MH - MicroRNAs/genetics/*metabolism MH - Middle Aged MH - RNA, Long Noncoding/genetics/metabolism MH - RNA, Messenger/genetics/metabolism MH - ROC Curve PMC - PMC7997347 OTO - NOTNLM OT - Nourin OT - acute coronary syndromes OT - inflammatory diagnostic biomarkers OT - miRNAs OT - reversible myocardial ischemia OT - unstable angina COIS- S.A.E. is the founder of Nour Heart, Inc. R.H.C. reports receiving a research grant from Spingotech Diagnostics, Roche Diagnostics, Siemens Diagnostics, Becton Dickinson. U.K. and D.L.K. are founders of Cell and Molecular Tissue Engineering, LLC. The other authors have no conflicts of interest to disclose. EDAT- 2021/03/07 06:00 MHDA- 2021/09/16 06:00 PMCR- 2021/02/28 CRDT- 2021/03/06 01:09 PHST- 2020/12/19 00:00 [received] PHST- 2021/01/19 00:00 [revised] PHST- 2021/02/23 00:00 [accepted] PHST- 2021/03/06 01:09 [entrez] PHST- 2021/03/07 06:00 [pubmed] PHST- 2021/09/16 06:00 [medline] PHST- 2021/02/28 00:00 [pmc-release] AID - biom11030368 [pii] AID - biomolecules-11-00368 [pii] AID - 10.3390/biom11030368 [doi] PST - epublish SO - Biomolecules. 2021 Feb 28;11(3):368. doi: 10.3390/biom11030368.