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Published on: January 28, 2020
Characterization of Systemic and Culprit-Coronary Artery miR-483-5p Expression in Chronic CAD and Acute Myocardial
Olga Volodko1,2, Natalia Volinsky1, Merav Yarkoni3
1The Lydia and Carol Kittner, Lea and Benjamin Davidai Division of Cardiovascular Medicine and Surgery and Research Institute, Tzafon Medical Center, Affiliated with Azrieli Faculty of Medicine, Bar Ilan University, Tiberias 1528001, Israel.
Insights
MicroRNA-483-5p shows a distinct coronary arterial gradient in acute myocardial infarction patients, differing from chronic coronary artery disease. This microRNA may serve as a biomarker and therapeutic target for cardiovascular diseases.
Area of Science:
- Cardiovascular Research
- Molecular Biology
- Genomics
Background:
- Coronary artery disease (CAD) is a leading global cause of mortality.
- Aberrant microRNA (miRNA) levels in circulation impact gene expression and pathophysiology in chronic and acute myocardial infarction (MI) states.
Purpose of the Study:
- To compare microRNA expression profiles in peripheral blood versus coronary arteries of male patients with chronic CAD and acute MI.
- To investigate the role of microRNA-483-5p (miR-483-5p) as a potential biomarker and therapeutic target in cardiovascular disease.
Main Methods:
- Blood samples were collected from peripheral arteries and proximal coronary arteries during coronary catheterization from chronic-CAD, acute-MI (STEMI/NSTEMI), and control patients.
- RNA extraction, miRNA library preparation, and Next Generation Sequencing were performed.
- In silico gene target analysis was conducted for miR-483-5p.
Main Results:
- A significant 'coronary arterial gradient' of miR-483-5p was observed in acute MI patients compared to chronic CAD patients (p = 0.035) and controls versus chronic CAD (p < 0.001).
- Peripheral miR-483-5p was downregulated in both acute MI and chronic CAD patients compared to controls (p < 0.005).
- Receiver operating characteristic curve analysis indicated miR-483-5p's association with chronic CAD (AUC = 0.722, p < 0.001), with 79% sensitivity and 70% specificity.
Conclusions:
- The high miR-483-5p coronary arterial gradient in acute MI suggests localized mechanisms in response to myocardial ischemia.
- MiR-483-5p targets genes involved in inflammation, oxidative stress, apoptosis, fibrosis, angiogenesis, and wound healing.
- MiR-483-5p is a potential biomarker and therapeutic target for acute and chronic cardiovascular diseases.
Abstract:
Coronary artery disease (CAD) is the leading cause of mortality worldwide. In chronic and myocardial infarction (MI) states, aberrant levels of circulating microRNAs compromise gene expression and pathophysiology. We aimed to compare microRNA expression in chronic-CAD and acute-MI male patients in peripheral blood vasculature versus coronary arteries proximal to a culprit area. Blood from chronic-CAD, acute-MI with/out ST segment elevation (STEMI/NSTEMI, respectively), and control patients lacking previous CAD or having patent coronary arteries was collected during coronary catheterization from peripheral arteries and from proximal culprit coronary arteries aimed for the interventions. Random coronary arterial blood was collected from controls; RNA extraction, miRNA library preparation and Next Generation Sequencing followed. High concentrations of microRNA-483-5p (miR-483-5p) were noted as 'coronary arterial gradient' in culprit acute-MI versus chronic-CAD (p = 0.035) which were similar to controls versus chronic-CAD (p < 0.001). Meanwhile, peripheral miR-483-5p was downregulated in acute-MI and chronic-CAD, compared with controls (1.1 ± 2.2 vs. 2.6 ± 3.3, respectively, p < 0.005). A receiver operating characteristic curve analysis for miR483-5p association with chronic CAD demonstrated an area under the curve of 0.722 (p < 0.001) with 79% sensitivity and 70% specificity. Using in silico gene analysis, we detected miR-483-5p cardiac gene targets, responsible for inflammation (PLA2G5), oxidative stress (NUDT8, GRK2), apoptosis (DNAAF10), fibrosis (IQSEC2, ZMYM6, MYOM2), angiogenesis (HGSNAT, TIMP2) and wound healing (ADAMTS2). High miR-483-5p 'coronary arterial gradient' in acute-MI, unnoticed in chronic-CAD, suggests important local mechanisms for miR483-5p in CAD in response to local myocardial ischemia. MiR-483-5p may have an important role as a gene modulator for pathologic and tissue repair states, is a suggestive biomarker, and is a potential therapeutic target for acute and chronic cardiovascular disease.
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