Cargando…

Nourin-Dependent miR-137 and miR-106b: Novel Biomarkers for Early Diagnosis of Myocardial Ischemia in Coronary Artery Disease Patients

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 “late” diagnosis. Additionally, the absence of a simple labora...

Descripción completa

Detalles Bibliográficos
Autores principales: Elgebaly, Salwa A., Christenson, Robert H., Kandil, Hossam, Ibrahim, Mohsen, Rizk, Hussien, El-Khazragy, Nashwa, Rashed, Laila, Yacoub, Beshoy, Eldeeb, Heba, Ali, Mahmoud M., Kreutzer, Donald L.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8070915/
https://www.ncbi.nlm.nih.gov/pubmed/33919942
http://dx.doi.org/10.3390/diagnostics11040703
_version_ 1783683579318894592
author Elgebaly, Salwa A.
Christenson, Robert H.
Kandil, Hossam
Ibrahim, Mohsen
Rizk, Hussien
El-Khazragy, Nashwa
Rashed, Laila
Yacoub, Beshoy
Eldeeb, Heba
Ali, Mahmoud M.
Kreutzer, Donald L.
author_facet Elgebaly, Salwa A.
Christenson, Robert H.
Kandil, Hossam
Ibrahim, Mohsen
Rizk, Hussien
El-Khazragy, Nashwa
Rashed, Laila
Yacoub, Beshoy
Eldeeb, Heba
Ali, Mahmoud M.
Kreutzer, Donald L.
author_sort Elgebaly, Salwa A.
collection PubMed
description 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 “late” 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 “reversible” 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 “pre-stress test” and “post-stress test” 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 “post-stress test” patients with CAD diagnosis showed upregulation of miR-137 by 572-fold and miR-106b-5p by 122-fold, when compared to negative “post-stress test” patients (p < 0.001); (3) similarly, positive “pre-stress test” CAD patients showed upregulation of miR-137 by 1198-fold and miR-106b-5p by 114-fold, when compared to negative “pre-stress test” patients (p < 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’ health outcome and save lives.
format Online
Article
Text
id pubmed-8070915
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-80709152021-04-26 Nourin-Dependent miR-137 and miR-106b: Novel Biomarkers for Early Diagnosis of Myocardial Ischemia in Coronary Artery Disease Patients Elgebaly, Salwa A. Christenson, Robert H. Kandil, Hossam Ibrahim, Mohsen Rizk, Hussien El-Khazragy, Nashwa Rashed, Laila Yacoub, Beshoy Eldeeb, Heba Ali, Mahmoud M. Kreutzer, Donald L. Diagnostics (Basel) Article 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 “late” 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 “reversible” 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 “pre-stress test” and “post-stress test” 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 “post-stress test” patients with CAD diagnosis showed upregulation of miR-137 by 572-fold and miR-106b-5p by 122-fold, when compared to negative “post-stress test” patients (p < 0.001); (3) similarly, positive “pre-stress test” CAD patients showed upregulation of miR-137 by 1198-fold and miR-106b-5p by 114-fold, when compared to negative “pre-stress test” patients (p < 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’ health outcome and save lives. MDPI 2021-04-14 /pmc/articles/PMC8070915/ /pubmed/33919942 http://dx.doi.org/10.3390/diagnostics11040703 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Elgebaly, Salwa A.
Christenson, Robert H.
Kandil, Hossam
Ibrahim, Mohsen
Rizk, Hussien
El-Khazragy, Nashwa
Rashed, Laila
Yacoub, Beshoy
Eldeeb, Heba
Ali, Mahmoud M.
Kreutzer, Donald L.
Nourin-Dependent miR-137 and miR-106b: Novel Biomarkers for Early Diagnosis of Myocardial Ischemia in Coronary Artery Disease Patients
title Nourin-Dependent miR-137 and miR-106b: Novel Biomarkers for Early Diagnosis of Myocardial Ischemia in Coronary Artery Disease Patients
title_full Nourin-Dependent miR-137 and miR-106b: Novel Biomarkers for Early Diagnosis of Myocardial Ischemia in Coronary Artery Disease Patients
title_fullStr Nourin-Dependent miR-137 and miR-106b: Novel Biomarkers for Early Diagnosis of Myocardial Ischemia in Coronary Artery Disease Patients
title_full_unstemmed Nourin-Dependent miR-137 and miR-106b: Novel Biomarkers for Early Diagnosis of Myocardial Ischemia in Coronary Artery Disease Patients
title_short Nourin-Dependent miR-137 and miR-106b: Novel Biomarkers for Early Diagnosis of Myocardial Ischemia in Coronary Artery Disease Patients
title_sort nourin-dependent mir-137 and mir-106b: novel biomarkers for early diagnosis of myocardial ischemia in coronary artery disease patients
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8070915/
https://www.ncbi.nlm.nih.gov/pubmed/33919942
http://dx.doi.org/10.3390/diagnostics11040703
work_keys_str_mv AT elgebalysalwaa nourindependentmir137andmir106bnovelbiomarkersforearlydiagnosisofmyocardialischemiaincoronaryarterydiseasepatients
AT christensonroberth nourindependentmir137andmir106bnovelbiomarkersforearlydiagnosisofmyocardialischemiaincoronaryarterydiseasepatients
AT kandilhossam nourindependentmir137andmir106bnovelbiomarkersforearlydiagnosisofmyocardialischemiaincoronaryarterydiseasepatients
AT ibrahimmohsen nourindependentmir137andmir106bnovelbiomarkersforearlydiagnosisofmyocardialischemiaincoronaryarterydiseasepatients
AT rizkhussien nourindependentmir137andmir106bnovelbiomarkersforearlydiagnosisofmyocardialischemiaincoronaryarterydiseasepatients
AT elkhazragynashwa nourindependentmir137andmir106bnovelbiomarkersforearlydiagnosisofmyocardialischemiaincoronaryarterydiseasepatients
AT rashedlaila nourindependentmir137andmir106bnovelbiomarkersforearlydiagnosisofmyocardialischemiaincoronaryarterydiseasepatients
AT yacoubbeshoy nourindependentmir137andmir106bnovelbiomarkersforearlydiagnosisofmyocardialischemiaincoronaryarterydiseasepatients
AT eldeebheba nourindependentmir137andmir106bnovelbiomarkersforearlydiagnosisofmyocardialischemiaincoronaryarterydiseasepatients
AT alimahmoudm nourindependentmir137andmir106bnovelbiomarkersforearlydiagnosisofmyocardialischemiaincoronaryarterydiseasepatients
AT kreutzerdonaldl nourindependentmir137andmir106bnovelbiomarkersforearlydiagnosisofmyocardialischemiaincoronaryarterydiseasepatients