2026-04-13T13:29:40Zhttps://recercat.cat/oai/request

oai:recercat.cat:11351/101232025-10-24T08:54:17Zcom_2072_378070com_2072_378040com_2072_378071col_2072_378092col_2072_378097

00925njm 22002777a 4500 dc Royo, Maria author Sandoval Moreno, Sebastian author Cortes Hernandez, Josefina author Solé, Cristina author Moline, Teresa author 2023-08-23T06:34:09Z 2023-08-23T06:34:09Z 2023-07-18 Antiphospholipid syndrome; Pathogenesis; Small extracellular vesicle Síndrome antifosfolípid; Patogènesi; Petita vesícula extracel·lular Síndrome antifosfolípido; Patogénesis; Pequeña vesícula extracelular Primary antiphospholipid syndrome (PAPS) is a systemic autoimmune disease associated with recurrent thrombosis and/or obstetric morbidity with persistent antiphospholipid antibodies (aPL). Although these antibodies drive endothelial injury and thrombophilia, the underlying molecular mechanism is still unclear. Small extracellular vesicles (sEVs) contain miRNAs, key players in intercellular communication. To date, the effects of miRNA-derived sEVs in PAPS are not well understood. We characterised the quantity, cellular origin and miRNA profile of sEVs isolated from thrombotic APS patients (PAPS, n = 50), aPL-carrier patients (aPL, n = 30) and healthy donors (HD, n = 30). We found higher circulating sEVs mainly of activated platelet origin in PAPS and aPL patients compared to HD, that were highly engulfed by HUVECs and monocyte. Through miRNA-sequencing analysis, we identified miR-483-3p to be differentially upregulated in sEVs from patients with PAPS and aPL, and miR-326 to be downregulated only in PAPS sEVs. In vitro studies showed that miR-483-3p overexpression in endothelial cells induced an upregulation of the PI3K-AKT pathway that led to endothelial proliferation/dysfunction. MiR-326 downregulation induced NOTCH pathway activation in monocytes with the upregulation of NFKB1, tissue factor and cytokine production. These results provide evidence that miRNA-derived sEVs contribute to APS pathogenesis by producing endothelial cell proliferation, monocyte activation and adhesion/procoagulant factors. http://hdl.handle.net/11351/10123 Síndrome antifosfolipídica MicroARN DISEASES::Immune System Diseases::Autoimmune Diseases::Antiphospholipid Syndrome ANATOMY::Cells::Cellular Structures::Extracellular Space::Extracellular Vesicles CHEMICALS AND DRUGS::Nucleic Acids, Nucleotides, and Nucleosides::Antisense Elements (Genetics)::RNA, Antisense::MicroRNAs ENFERMEDADES::enfermedades del sistema inmune::enfermedades autoinmunes::síndrome antifosfolípido ANATOMÍA::células::estructuras celulares::espacio extracelular::vesículas extracelulares COMPUESTOS QUÍMICOS Y DROGAS::nucleótidos y nucleósidos de ácidos nucleicos::elementos antisentido (genética)::ARN antiparalelo::microARN Small-Extracellular-Vesicle-Derived miRNA Profile Identifies miR-483-3p and miR-326 as Regulators in the Pathogenesis of Antiphospholipid Syndrome (APS)