Integrative analysis of miRNAs and proteins in plasma extracellular vesicles of patients with familial hypercholesterolemia

•FH is an autosomal dominant disorder causing high LDL and premature atherosclerosis;•20–40 % of patients lack causative mutations in FH genes like LDLR, APOB, PCSK9;•miR-122-5p is highly expressed in FH patients compared to control;•miR-21-5p is associated with the severity of the disease;•Integrative analysis of EV miRNAs and proteins may aid FH diagnosis and therapy; Familial Hypercholesterolemia (FH) is a monogenic disease that leads to early-onset atherosclerosis. Causative mutations in FH-related genes are found in 60–80 % of patients, while epigenetic factors may contribute to mutation-negative cases. This study analyzed miRNAs and proteins from plasma-derived extracellular vesicles (EVs) of FH patients to explore their contribution in FH diagnosis. Clinical and laboratory data were obtained from 54 FH patients and 38 normolipidemic individuals. FH-related gene variants were identified using exon-targeted gene sequencing. Plasma EVs miRNome and proteome were analysed using small RNA sequencing and liquid chromatography/mass spectrometry. Thirteen FH patients carried LDLR deleterious variants (MD group), while 41 did not (non-MD group). Over 2000 miRNAs were detected in plasma EVs, with miR-122-5p higher in FH patients compared to controls, and miR-21-5p higher in the MD group than in the non-MD group (p