Related Experiment Video
Updated: Oct 11, 2025
In Vivo Nanovector Delivery of a Heart-specific MicroRNA-sponge
Published on: June 15, 2018
AIFM1, negatively regulated by miR-145-5p, aggravates hypoxia-induced cardiomyocyte injury
Wugang Zhou1, Lv Ji2, Xuqin Liu2
1Department of Emergency, Shanghai Ninth People's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China; Department of Intensive Care Unit, Shigatse People's Hospital, Shigatse, Tibet Autonomous Region, China.
Background:
Hypoxia-induced apoptosis is linked to the pathogenesis of myocardial infarction. The role of apoptosis-inducing factor mitochondria associated 1 (AIFM1) in cardiomyocyte injury remains unclear. This study was aimed at probing into the role and the underlying regulatory mechanism of AIFM1 in myocardial injury.
Methods:
H9c2 cardiomyocytes and C57BL/6 mice were used for myocardial hypoxic/ischemic injury and myocardial infarction animal models. Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to evaluate the expression levels of AIFM1 mRNA and miR-145-5p. Western blot was used for examining the expression levels of AIFM1, caspase-3, cleaved caspase-3, p-53, and γ-H2AX. Cell viability was examined by cell counting kit-8 (CCK-8) assay and BrdU assay. Interaction between AIFM1 and miR-145-5p was determined by bioinformatics analysis, qRT-PCR, Western blot, and dual-luciferase reporter assay.
Results:
AIFM1 expression was markedly highly elevated, while miR-145-5p expression was significantly down-regulated in the myocardial infarction animal model and H9c2 cells under hypoxia. Augmentation of AIFM1 led to a dramatic decrease of cell viability, accompanied by an increase of the secretion of the inflammatory cytokines IL-1β, TNF-α, IL-6, and the expression of cleaved caspase-3. Furthermore, AIFM1 was identified as a target of miR-145-5p. In addition, miR-145-5p/AIFM1 axis regulated the expression of p53.
Conclusion:
AIFM1 may exacerbate myocardial ischemic injury by promoting inflammation and the injury of cardiomyocytes, and its up-regulation may be partly due to the down-regulation of miR-145-5p.
Insights
Apoptosis-inducing factor mitochondria associated 1 (AIFM1) exacerbates myocardial infarction by promoting inflammation and cardiomyocyte injury. Its upregulation is linked to decreased miR-145-5p levels, suggesting a novel therapeutic target for heart attack.
Area of Science:
- Cardiovascular Biology
- Molecular Medicine
- Cellular Pathology
Background:
- Hypoxia-induced apoptosis is a key factor in myocardial infarction pathogenesis.
- The specific role of apoptosis-inducing factor mitochondria associated 1 (AIFM1) in cardiomyocyte injury is not well understood.
Purpose of the Study:
- To investigate the role of AIFM1 in myocardial injury.
- To elucidate the regulatory mechanism of AIFM1 in the context of myocardial infarction.
Main Methods:
- Utilized H9c2 cardiomyocytes and a mouse model of myocardial infarction.
- Assessed AIFM1 and miR-145-5p expression via qRT-PCR and protein levels via Western blot.
- Evaluated cell viability and apoptosis markers, and confirmed the interaction between AIFM1 and miR-145-5p.
Main Results:
- AIFM1 expression was significantly upregulated, while miR-145-5p was downregulated in myocardial infarction models.
- Increased AIFM1 reduced cell viability and increased inflammatory markers and cleaved caspase-3.
- AIFM1 was identified as a direct target of miR-145-5p, and the miR-145-5p/AIFM1 axis influenced p53 expression.
Conclusions:
- AIFM1 exacerbates myocardial ischemic injury by promoting inflammation and cardiomyocyte damage.
- Upregulation of AIFM1 may be partly attributed to the downregulation of miR-145-5p, highlighting a potential therapeutic pathway.
Related Concept Videos
01:21Myocarditis I: Introduction
01:24Regulation of Angiogenesis and Blood Supply