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Dagli-Hernandez, Carolina ; de Freitas, Renata Caroline Costa ; Luchessi, Andre Ducati ; Hirata, Thiago Dominguez Crespo ; Fajardo, Cristina Moreno ; Borges, Jessica Bassani ; de Oliveira, Victor Fernandes ; Neta, Antonia Pereira Rosa ; Faludi, Andre Arpad ; Goncalves, Rodrigo Marques ; Bortolin, Raul Hernandes ; Malaquias, Vanessa Barbosa ; Bastos, Gisele Medeiros ; Sampaio, Marcelo Ferraz ; Hirata, Mario Hiroyuki ; Hirata, Rosario Dominguez Crespo

• Tipo de documento: Artigo Científico
• Fonte: Journal of Pharmacology and Experimental Therapeutics; v. 392, n. 7, p. 11-pg., 2025-07-01.

Resumo

MicroRNAs (miRNAs) contribute to the variability in statin response by modulating genes involved in lipid metabolism. However, no studies evaluating exosomal miRNA profiles after statin treatment in patients with familial hypercholesterolemia (FH) have been performed. This study aimed to explore the effects of short-term statin treatment on the miRNA profile of plasma exosomes from patients with FH. Thirty-eight patients with FH on 6-week statin treatment and 32 normolipidemic subjects (control group) were selected. Plasma exosomes were isolated, and miRNA expression was analyzed by small RNA sequencing. Enrichment analysis was used to identify miRNA targets, interactions, and pathways. Expression of let-7a, miR-16, miR-92a, miR-122, and miR-486a was higher in the FH group than in the control group (fold change, >=+/- 1.5; P < .05). Statin treatment upregulated miR-92a and downregulated let-7b and miR-423 (P < .05) in plasma exosomes from patients with FH. In the overall group, baseline levels (normalized counts) of let-7a, miR-16, miR-92a, miR-122, and miR-486 were positively correlated with total and low-density lipoprotein cholesterol, triglycerides, and apolipoprotein B and inversely correlated with high-density lipoprotein cholesterol (P < .05). Let-7b and miR-423 were also correlated with total cholesterol and triglycerides. The FH- and statin-dysregulated miRNAs target genes involved in cell cycle and proliferation, protein catabolism, and other biological processes, in addition to cholesterol homeostasis and cardiovascular function. In conclusion, FH and statin treatment alter the profile of plasma exosome-derived miRNAs, which have potential application as biomarkers for FH assessment and statin treatment monitoring. Future studies with larger cohorts, extended treatment periods, and validation via quantitative polymerase chain reaction are warranted to elucidate the role of these miRNAs in FH and statin response. (AU)

• Processo FAPESP: 16/12899-6 - Caracterização genômica, epigenômica e farmacogenômica de portadores de hipercolesterolemia familial na população brasileira
• Beneficiário: Mario Hiroyuki Hirata
• Modalidade de apoio: Auxílio à Pesquisa - Temático