Related Experiment Video
Updated: Sep 5, 2025
Analysis of Combinatorial miRNA Treatments to Regulate Cell Cycle and Angiogenesis
Published on: March 30, 2019
The mir-21 Inhibition Enhanced HUVEC Cellular Viability during Hypoxia-Reoxygenation Injury by Regulating PDCD4
1Department of Internal Medicine, College of Medicine, Jouf University, Sakaka, Saudi Arabia.
Insights
Plasma miR-21 levels indicate coronary artery disease (CAD) severity and impact endothelial cells. Higher miR-21 correlates with CAD extent and aging, offering a potential biomarker and therapeutic target for CAD.
Area of Science:
- Molecular biology and cardiology
- Biomarker discovery for cardiovascular disease
Background:
- Coronary artery disease (CAD) poses a significant global health challenge.
- Identifying reliable biomarkers for CAD severity is crucial for effective management.
- MicroRNAs (miRNAs) are emerging as key regulators in cardiovascular pathophysiology.
Purpose of the Study:
- To investigate the clinical utility of plasma miR-21 as a biomarker for CAD severity.
- To explore the molecular mechanisms of miR-21 in hypoxia-reoxygenation (HR)-induced HUVEC injury.
- To assess the potential of miR-21 as a therapeutic target in CAD.
Main Methods:
- Plasma miR-21 and PDCD4 levels were quantified in 343 participants (CAD patients and healthy controls).
- Human Umbilical Vein Endothelial Cells (HUVECs) were subjected to hypoxia-reoxygenation (HR) in vitro.
- miR-21 expression, PDCD4 levels, caspase-3 activity, ROS production, and cellular viability were assessed.
- miR-21 inhibition was performed to evaluate its therapeutic potential.
Main Results:
- Plasma miR-21 levels progressively increased with CAD severity (single-, double-, and multivessel disease) and correlated positively with aging.
- PDCD4 levels showed a reciprocal decrease with increasing CAD severity and miR-21 upregulation.
- HR-exposed HUVECs exhibited elevated miR-21, caspase-3, and ROS, with reduced PDCD4 and viability.
- miR-21 inhibition in HR-HUVECs decreased caspase-3 and ROS, enhanced PDCD4, and improved cellular viability.
Conclusions:
- Plasma miR-21 is a sensitive and specific biomarker for detecting CAD severity.
- Upregulated miR-21 contributes to endothelial cell injury in CAD, partly via PDCD4 downregulation.
- Inhibiting miR-21 demonstrates therapeutic potential for managing CAD by protecting endothelial cells.
Abstract:
The purpose of this study was to explore the clinical value of altered plasma mir-21 expression level as a biomarker for the severity of coronary artery disease (CAD) and its molecular impact on HUVEC cellular injuries. Angiographically validated 56 patients with single-vessel CAD disease, 92 patients with double-vessel CAD, 139 complex coronary artery stenosis patients, and 56 healthy individuals (n = 343) were enrolled in this study. The expressions of plasma mir-21 were evidently and progressively higher while PDCD4 levels were significantly and steadily lower in single-, dual-, and multivessel occluded CAD patients than in healthy participants (P < 0.001). The relative expressions of mir-21 in hypoxia-reoxygenation- (HR-) exposed HUVECs were markedly upregulated, but PDCD4 concentrations were obviously downregulated as compared with normal control cells (P < 0.001). Moreover, altered circulatory mir-21 expression levels were able to significantly differentiate single- (AUC 0.893), double- (AUC 0.914), and multivessel stenosis CAD (AUC 0.933) patients from healthy subjects. Besides, the plasma mir-21 expressions in elderly (66-85 years) groups were remarkably higher than those in younger aged (25-45 years) subjects. Caspase-3 and ROS expression levels were remarkably elevated, but cellular viability noticeably declined in HR-induced HUVECs than in normoxic cells (P < 0.001). In contrast, mir-21 inhibition markedly reduced caspase-3 activity and ROS concentrations while significantly ameliorating HUVEC cellular viability in HR conditions. PDCD4 expressions in HR-exposed HUVECs were prominently decreased whereas mir-21 inhibition significantly enhanced PDCD4 levels (P < 0.001). Upregulated plasma mir-21 can be a valuable clinical biomarker for the detection of the severity of coronary artery stenosis patients. Elevated circulatory mir-21 concentrations have a positive correlation with aging. Inhibitory mir-21 evidently increased HUVEC cellular viability through upregulation of targeting PDCD4 and recommended a newer possible therapeutic molecule for the management of CAD patients.
More Related Videos
Related Concept Videos
01:24Regulation of Angiogenesis and Blood Supply
01:23Hypoxia
Types of Hypoxia
There are four primary types of hypoxia, each resulting from a different cause:
1. Anemic hypoxia: This type occurs due to insufficient oxygen delivery caused by a lack of red blood cells (RBCs) or RBCs with abnormal or...
02:49Cancer Therapies
However, cancer treatments can pose several challenges, as therapies used to kill cancer cells are generally also toxic to normal cells. Moreover, cancer cells mutate rapidly and can develop resistance to chemical agents or radiation therapy. Besides, all types of cancer cells may not respond to the same therapy. Some cancer cells respond to one...