Characterization of Antiphospholipid Syndrome Atherothrombotic Risk by Unsupervised Integrated Transcriptomic Analyses

Objective: Our aim was to characterize distinctive clinical antiphospholipid syndrome phenotypes and identify novel microRNA (miRNA)-mRNA-intracellular signaling regulatory networks in monocytes linked cardiovascular disease. Approach Results: Microarray analysis revealed 547 differentially expressed genes, mainly involved inflammatory, cardiovascular, reproductive disorders. Besides, this approach identified several genes related renal, dermatologic diseases. Functional analyses further demonstrated phosphorylation of intracellular kinases thrombosis immune-mediated chronic inflammation. miRNA profiling showed altered expression 22 miRNAs, enriched pathways immune functions, disease, autoimmune-associated pathologies. Unbiased integrated mRNA-miRNA a signature 9 miRNAs as potential modulators 17 interconnected The that miRNA-mRNA proven be stable along time nonautoimmune thrombotic patients. Transfection studies luciferase assays established the relationship between specific their target proteins, with involvement regulation procoagulant activity cell adhesion. Correlation among aPL (antiphospholipid antibodies)-titers, microvascular endothelial dysfunction. In vitro modulation healthy by IgG-aPLs genes/miRNAs, which intermediated downstream effects on function. transcriptomic allowed unsupervised division three clusters patients showing profiles, associated prothrombotic risk (thrombosis, autoantibody profile, factors, atherosclerosis). Conclusions: Extensive molecular primary might help phenotypes, thus enabling new patients’ tailored treatments.