Characterization of Systemic and Culprit-Coronary Artery miR-483-5p Expression in Chronic CAD and Acute Myocardial Infarction Male Patients.
Olga VolodkoNatalia VolinskyMerav YarkoniNufar MargalitFabio KusniecDoron SudarskyGabby Elbaz-GreenerShemy CarassoOffer AmirPublished in: International journal of molecular sciences (2023)
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.
Keyphrases
- coronary artery disease
- coronary artery
- percutaneous coronary intervention
- cardiovascular events
- drug induced
- liver failure
- oxidative stress
- coronary artery bypass grafting
- gene expression
- cardiovascular disease
- acute myocardial infarction
- respiratory failure
- ejection fraction
- newly diagnosed
- copy number
- left ventricular
- end stage renal disease
- aortic stenosis
- poor prognosis
- peripheral blood
- pulmonary artery
- type diabetes
- extracorporeal membrane oxygenation
- patient reported
- st elevation myocardial infarction
- intensive care unit
- neoadjuvant chemotherapy
- circulating tumor cells
- cell proliferation
- long non coding rna
- wound healing
- heat shock protein
- pulmonary hypertension
- tandem mass spectrometry
- ischemia reperfusion injury
- liquid chromatography
- induced apoptosis