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Herbal Munziq Ameliorates Myocardial Ischemia-Reperfusion Injury by Inhibiting Inflammation
Published on: January 10, 2025
CircBAZ1B stimulates myocardial ischemia/reperfusion injury (MI/RI) by modulating miR-1252-5p/ATF3-mediated
Ruili Wei1, Tianxiao Yang1, Weihong Li1
1Department of Cardiovascular Medicine, Zibo Central Hospital, Zibo, Shandong, China.
Introduction:
Circular RNAs (circRNAs) have been implicated in myocardial ischemia (MI)/reperfusion injury (RI), yet their essential roles in MI/RI-induced ferroptosis have not been fully elucidated. Here, we focused on the biological function and regulatory mechanism of circBAZ1B, a circRNA derived from the bromodomain adjacent to the zinc finger domain 1B (BAZ1B) gene, in MI/RI progression.
Material And Methods:
We used a rat model for MI/RI, assessing myocardial infarct size via electrocardiogram (ECG) and histological staining (hematoxylin and eosin [H&E] and 2,3,5-triphenyltetrazolium chloride [TTC]). Rat cardiomyoblasts (H9c2) were used for in vitro hypoxia-reoxygenation (H/R) cell model construction. Cell viability, apoptosis, lipid reactive oxygen species (ROS) levels and iron content were determined via Cell Counting Kit-8 (CCK-8) and flow cytometric assays. Gene and ferroptosis-related protein expression levels were verified by qRT-PCR and Western blotting. RNA pull-down, RNA immunoprecipitation (RIP), and a dual-luciferase reporter system were utilized for verification of the molecular interactions.
Results:
The results showed that MI/RI was accompanied by ferroptosis. We also found that activating transcription factor 3 (ATF3) knockdown promoted myocardial cell viability and inhibited ferroptosis. Notably, activation of ATF3 transcription was demonstrated to upregulate the expression of its downstream target ACSL4. Functional analysis indicated that circBAZ1B promoted ATF3 expression via miR-1252-5p. In vivo experimental data further revealed that circBAZ1B suppressed cardiomyocyte activity and promoted ferroptosis, thereby facilitating MI/RI progression.
Conclusions:
The circBAZ1B/miR-1252-5p/ATF3 axis is crucial in MI/RI pathogenesis through ferroptosis regulation, offering a potential therapeutic target. Inhibiting this pathway may alleviate MI/RI effects, suggesting the need for further clinical studies.
Insights
Circular RNA BAZ1B (circBAZ1B) exacerbates myocardial ischemia/reperfusion injury by promoting ferroptosis through the miR-1252-5p/ATF3 pathway. Inhibiting this axis may offer a therapeutic strategy for heart injury.
Area of Science:
- Cardiovascular Biology
- Molecular Medicine
- Cell Death Pathways
Background:
- Circular RNAs (circRNAs) are implicated in myocardial ischemia (MI)/reperfusion (RI) injury.
- The role of circRNAs in MI/RI-induced ferroptosis remains largely unknown.
- This study investigates circBAZ1B's function in MI/RI progression.
Purpose of the Study:
- To elucidate the biological function and regulatory mechanism of circBAZ1B in myocardial ischemia/reperfusion injury.
- To investigate the role of circBAZ1B in ferroptosis during MI/RI.
- To identify potential therapeutic targets for MI/RI.
Main Methods:
- Established rat MI/RI and H9c2 hypoxia-reoxygenation (H/R) cell models.
- Assessed infarct size, cell viability, apoptosis, and ferroptosis markers (ROS, iron content).
- Utilized qRT-PCR, Western blotting, RNA pull-down, RIP, and dual-luciferase assays to determine molecular interactions.
Main Results:
- MI/RI induced ferroptosis, and circBAZ1B promoted this process.
- circBAZ1B upregulated activating transcription factor 3 (ATF3) via miR-1252-5p, enhancing ferroptosis.
- Knockdown of ATF3 improved cell viability and inhibited ferroptosis in MI/RI models.
Conclusions:
- The circBAZ1B/miR-1252-5p/ATF3 axis is critical in MI/RI pathogenesis by regulating ferroptosis.
- Targeting this pathway presents a potential therapeutic strategy for alleviating MI/RI.
- Further clinical studies are warranted to explore therapeutic interventions.
