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Methamphetamine use alters human plasma extracellular vesicles and their microRNA cargo: An exploratory study
Ursula S Sandau1, Erika Duggan2, Xiao Shi3,4,5,6
1Department of Anesthesiology & Perioperative Medicine Oregon Health & Science University Portland Oregon USA.
Abstract:
Methamphetamine (MA) is the largest drug threat across the globe, with health effects including neurotoxicity and cardiovascular disease. Recent studies have begun to link microRNAs (miRNAs) to the processes related to MA use and addiction. Our studies are the first to analyse plasma EVs and their miRNA cargo in humans actively using MA (MA-ACT) and control participants (CTL). In this cohort we also assessed the effects of tobacco use on plasma EVs. We used vesicle flow cytometry to show that the MA-ACT group had an increased abundance of EV tetraspanin markers (CD9, CD63, CD81), but not pro-coagulant, platelet-, and red blood cell-derived EVs. We also found that of the 169 plasma EV miRNAs, eight were of interest in MA-ACT based on multiple statistical criteria. In smokers, we identified 15 miRNAs of interest, two that overlapped with the eight MA-ACT miRNAs. Three of the MA-ACT miRNAs significantly correlated with clinical features of MA use and target prediction with these miRNAs identified pathways implicated in MA use, including cardiovascular disease and neuroinflammation. Together our findings indicate that MA use regulates EVs and their miRNA cargo, and support that further studies are warranted to investigate their mechanistic role in addiction, recovery, and recidivism.
Insights
Methamphetamine (MA) use alters plasma extracellular vesicles (EVs) and their microRNA (miRNA) cargo. These changes may play a role in MA addiction and its associated health risks.
Area of Science:
- Neuroscience
- Biochemistry
- Genetics
Background:
- Methamphetamine (MA) is a global drug threat, causing neurotoxicity and cardiovascular disease.
- MicroRNAs (miRNAs) are increasingly linked to MA use and addiction.
- Plasma extracellular vesicles (EVs) and their miRNA cargo in active MA users are underexplored.
Purpose of the Study:
- To analyze plasma EVs and their miRNA cargo in active MA users versus controls.
- To investigate the effects of tobacco use on plasma EVs in this cohort.
- To identify specific miRNAs associated with MA use and their potential clinical relevance.
Main Methods:
- Vesicle flow cytometry was used to quantify EV markers.
- Plasma EV miRNAs were analyzed using next-generation sequencing.
- Statistical criteria identified significant miRNAs associated with MA use and smoking.
- miRNA target prediction and pathway analysis were performed.
Main Results:
- Active MA users (MA-ACT) showed increased abundance of EV tetraspanin markers (CD9, CD63, CD81).
- Eight plasma EV miRNAs were significantly associated with MA-ACT.
- Fifteen miRNAs were associated with smoking, with two overlapping with MA-associated miRNAs.
- Three MA-associated miRNAs correlated with clinical features and implicated pathways like cardiovascular disease and neuroinflammation.
Conclusions:
- MA use significantly alters plasma EV composition and miRNA cargo.
- Specific miRNAs are associated with MA use and may contribute to its health effects.
- Further research into the mechanistic role of these EV miRNAs in MA addiction, recovery, and recidivism is warranted.
