MicroRNA-21 Protects Hypoxic-Induced Cardiomyocytes Injury by Targeting Smad-7

Area of Science:

• Cardiovascular Research
• Molecular Biology
• Biomarker Discovery

Background:

• Acute myocardial infarction (AMI) is a leading cause of sudden cardiac death globally.
• Understanding the molecular mechanisms and diagnostic markers of AMI is crucial for improving patient outcomes.

Purpose of the Study:

• To investigate the diagnostic role of plasma miR-21, miR-488, and miR-126 in patients with acute myocardial infarction (AMI).
• To explore the molecular impact of miR-21 inhibition on hypoxia-induced cellular injury in H9c2 cells.
• To assess the potential of these microRNAs as clinical biomarkers for AMI.

Main Methods:

• Analysis of plasma microRNA levels in 95 non-ST-elevation myocardial infarction (NSTEMI) patients, 152 ST-elevation myocardial infarction (STEMI) patients, and 95 healthy controls.
• Utilized three-month-old mice and ventricular-derived H9c2 cells for cellular studies.
• Employed receiver operating characteristic (ROC) curve analysis for diagnostic assessment and in vitro experiments with miR-21 inhibitors on H9c2 cells.

Main Results:

• Plasma miR-21 and miR-488 levels were significantly upregulated, while miR-126 levels were downregulated in NSTEMI and STEMI patients compared to healthy individuals.
• ROC curve analysis confirmed the diagnostic capability of these microRNAs in differentiating AMI patients from controls.
• Inhibition of miR-21 in H9c2 cells reduced reactive oxygen species (ROS), caspase-3 activity, and apoptosis, while enhancing viability by upregulating Smad-7 expression.

Conclusions:

• Circulating miR-21, miR-488, and miR-126 are potential biomarkers for diagnosing AMI.
• Inhibition of miR-21 presents a promising therapeutic strategy for AMI by mitigating hypoxia-induced cellular damage through Smad-7 targeting.
• Elevated plasma miR-21 levels in geriatric AMI patients warrant further investigation, and low miR-21 may impact aging processes.