Differentially expressed miRNA profiles of serum derived extracellular vesicles from patients with acute ischemic stroke

• Published in: Brain research Vol. 1845; p. 149171
• Main Authors: Pir, Ghulam Jeelani, Zahid, Muhammad Ammar, Akhtar, Naveed, Ayadathil, Raheem, Pananchikkal, Sajitha V., Joseph, Sujata, Morgan, Deborah M., Babu, Blessy, Ty Ui, Ryan, Sivasankaran, Shobhna, Francis, Reny, Own, Ahmed, Shuaib, Ashfaq, Parray, Aijaz, Agouni, Abdelali
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 15.12.2024
• Subjects: Aged; Biomarkers - blood; Biomarkers - metabolism; Brain; Brain Ischemia - blood; Brain Ischemia - genetics; Brain Ischemia - metabolism; Extracellular vesicles; Extracellular Vesicles - metabolism; Female; Gene Expression Profiling - methods; Humans; Ischemia; Ischemic Stroke - blood; Ischemic Stroke - genetics; Ischemic Stroke - metabolism; Male; MicroRNAs - blood; MicroRNAs - genetics; MicroRNAs - metabolism; Middle Aged; miRNAs; Neurology; Stroke; Stroke - blood; Stroke - genetics; Stroke - metabolism; CRP; APP; Brain; RT; BBB; miRNAs; MoCA; MRI; Extracellular vesicles; ASA; Ischemia; FDR; DABG; PBS; MCAO; NIHSS; Stroke; EVs; AD; ESR; RMA; GO; AIS; PBMCs; ICH; RA; mRS; GEO; BACE1; CT; BLIMP-1; RF; DALYs; AV; MMVEC; miEAA; AHA; IPA; ORA; C-reactive protein; Montreal Cognitive Assessment; B lymphocyte-induced maturation protein-1; Gene Expression Omnibus; Computed tomography; Blood-brain barrier; Modified Rankin Scale; American Stroke Association; Erythrocyte sedimentation rate; National Institute of Health Stroke Scale; Gene Ontology; Ingenuity Pathway Analysis; Alzheimer’s disease; Extracellular vehicles; American Heart Association; Magnetic Resonance Imaging; Acute ischemic stroke; Rheumatoid arthritis; Disability-adjusted life years; Detection Above Background; Myocardial microvascular endothelial cells; Robust multi-array average; Peripheral blood mononuclear cells; miRNA Enrichment Analysis and Annotation; Phosphate-buffered saline; Over-representation analysis; Arteriovenous; Middle cerebral artery occlusion; Amyloid precursor protein; β-site amyloid precursor protein-cleaving enzyme 1; Rheumatoid factor; MicroRNAs; False discovery rate; Intracranial haemorrhage; Room temperature
• ISSN: 0006-8993; 1872-6240; 1872-6240
• DOI: 10.1016/j.brainres.2024.149171

[Display omitted] •Five circulating EV-miRNAs were differentially expressed in acute ischemic stroke.•Novel downregulation of hsa-miR-548a-3p and hsa-miR-6808-3p was observed in stroke.•EV-miRNAs implicate key pathways including RNA transport, autophagy, and cell cycle.•Findings reveal potential biomarkers for stroke diagnosis and therapeutic strategies.•Study provides insights into molecular mechanisms of stroke pathology. 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. 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. 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. 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.