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Published on: September 5, 2016
Platelet-Derived Microvesicles Mediate Cardiomyocyte Ferroptosis by Transferring ACSL1 During Acute Myocardial
Yunfeng Zhao1, Rui Cui1, Ran Du1
1Department of Cardiology, First Hospital of Qinhuangdao, No. 258, Wenhua Road, Haigang District, Qinhuangdao, 066099, China.
Insights
Platelet-derived microvesicles (PMVs) carrying ACSL1 can trigger cardiomyocyte death via ferroptosis in acute myocardial infarction (AMI). Targeting platelet ACSL1 may offer a new strategy to treat AMI by reducing ferroptosis.
Area of Science:
- Cardiovascular Biology
- Cellular Signaling
- Molecular Medicine
Background:
- Acute myocardial infarction (AMI) involves cardiomyocyte death, with the role of platelet-derived microvesicles (PMVs) unclear.
- Ferroptosis, a regulated cell death pathway, is implicated in AMI pathogenesis.
- Understanding PMV-mediated communication is crucial for developing novel therapeutic strategies.
Purpose of the Study:
- To investigate the role of PMVs in AMI-induced cardiomyocyte death.
- To identify key molecular players and regulatory networks involved in PMV-mediated ferroptosis in AMI.
- To explore potential therapeutic targets for mitigating ferroptosis in AMI.
Main Methods:
- Analysis of AMI-related mRNA and miRNA datasets from the GEO database, focusing on ferroptosis-associated genes.
- Construction of a miRNA-mRNA regulatory network specific to AMI.
- In vitro experiments using PMVs and AC16 cardiomyocytes to assess the impact on cell survival and ferroptosis.
- Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses.
Main Results:
- High ACSL1 expression was detected in platelets of AMI patients.
- ACSL1, localized in mitochondria, is involved in the PPAR signaling pathway.
- Elevated ACSL1 expression in PMVs significantly increased ferroptosis in cardiomyocytes.
- hsa-miR-449a was identified as a regulator of platelet ACSL1 expression.
Conclusions:
- Platelet ACSL1, transported via PMVs, can induce cardiomyocyte ferroptosis, contributing to AMI pathogenesis.
- This study provides a theoretical basis for targeting platelet ACSL1 and PMV-mediated ferroptosis in AMI treatment.
- The findings highlight a novel mechanism of cell death in AMI and suggest potential therapeutic avenues.
Abstract:
Acute myocardial infarction (AMI) is one of the critical health conditions often caused by the rupture of unstable coronary artery plaque, triggering a series of events, such as platelet activation, thrombus formation, coronary artery blockage, lasted severe ischemia, and hypoxia in cardiomyocytes, and culminating in cell death. Platelet-derived microvesicles (PMVs) act as intermediates for cellular communication. Nevertheless, the role of PMVs in myocardial infarction remains unclear. Initially, AMI-related messenger ribose nucleic acid (mRNA) and micro RNA (miRNA) datasets from the Gene Expression Omnibus (GEO) database were analyzed, specifically focusing on the expressed genes associated with Ferroptosis. Further, a miRNA-mRNA regulatory network specific to AMI was constructed. Then, the effect of PMVs on cardiomyocyte survival was further confirmed through in vitro experiments. High ACSL1 expression was observed in the platelets of AMI patients. The gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses revealed that ACSL1, located in the mitochondria, played a key role in the PPAR signaling pathway. The elevated ACSL1 expression in a co-culture model of PMVs and AC16 cardiomyocytes significantly increased the AC16 cell Ferroptosis. Further, we validated that the platelet ACSL1 expression could be regulated by hsa-miR-449a. Together, these findings suggested that platelet ACSL1 could trigger myocardial cell death via PMV transport. In addition, this research provided a theoretical framework for attenuating myocardial cell Ferroptosis in patients with acute myocardial infarction.
