RESUMEN
BACKGROUND: MicroRNAs (miRNAs) participate in diverse cellular changes following acute ischemic stroke (AIS). Circulating miRNAs, stabilized and delivered to target cells via extracellular vesicles (EVs), are potential biomarkers to facilitate diagnosis, prognosis, and therapeutic modulation. We aimed to identify distinctive expression patterns of circulating EV-miRNAs in AIS patients. METHODS: miRNA profiles from EVs, isolated from plasma samples collected within 24 h following AIS diagnosis, were examined between a dataset of 10 age-, gender- and existing comorbidities-matched subjects (5 AIS and 5 healthy controls, HC). We measured 2578 miRNAs and identified differentially expressed miRNAs between AIS and HC. An enrichment analysis was conducted to delineate the networks and biological pathways implicated by differentially expressed microRNAs. An enrichment analysis was conducted to delineate the networks and biological pathways implicated by differentially expressed microRNAs. RESULTS: Five miRNAs were differentially expressed between stroke (AIS) versus control (HC). hsa-let-7b-5p, hsa-miR-16-5p, and hsa-miR-320c were upregulated, whereas hsa-miR-548a-3p and hsa-miR-6808-3p, with no previously reported changes in stroke were downregulated. The target genes of these miRNAs affect various cellular pathways including, RNA transport, autophagy, cell cycle progression, cellular senescence, and signaling pathways like mTOR, PI3K-Akt, and p53. Key hub genes within these networks include TP53, BCL2, Akt, CCND1, and NF-κB. These pathways are crucial for cellular function and stress response, and their dysregulation can have significant implications for the disease processes. CONCLUSION: Our findings reveal distinct circulating EV-miRNA expression patterns in AIS patients from Qatar, highlighting potential biomarkers that could aid in stroke diagnosis and therapeutic strategies. The identified miRNAs are involved in critical cellular pathways, offering novel insights into the molecular mechanisms underlying stroke pathology. Circulating EV-miRNAs differentially expressed in AIS may have a pathophysiological role and may guide further research to elucidate their precise mechanisms.
RESUMEN
Stroke attacks were found to be present at a younger age in patients from Southeast Asia (SE) and the Middle East (ME) resident in the state of Qatar. Extracellular vesicles (EVs), which are small membrane vesicles with pro-thrombotic properties, may contribute to the high risk of stroke in this population. Thus, total and cell-specific medium size EVs were counted by flow cytometry in platelet-free plasma from healthy volunteers and patients with transient ischemic attacks (TIA) and acute ischemic stroke (AIS) from SE and ME. Acutely, within 48 h of attacks, there was an increase in total endothelial EVs in TIA (6.73 ± 1.77; P = 0.0156; n = 21) and AIS (11.23 ± 1.95; P = 0.0007; n = 66) patients compared to controls (2.04 ± 0.78; n = 24). Similar increases were also evident in EVs originating from platelets, erythrocytes, granulocytes, and leukocytes. Compared to controls, there was also an increase in EVs derived from activated endothelial cells, platelets, granulocytes, leukocytes, and pro-coagulant EVs (Annexin V+) at 5 and 30-days following the acute events, while a decrease was observed in erythrocyte-derived EVs. This is the first study characterizing EVs in TIA and AIS patients from ME and SE showing an increase in EVs associated with endothelial and platelet cell activation, which may contribute to the elevated risk of stroke at a younger age in this population.