Circulating microRNAs In Hereditary Hemorrhagic Telangiectasia: Preliminary Results Identify Significant Differences Among Patients

Objectives: We are investigating the role of circulating microRNAs (miRNAs) in HHT as potential disease biomarkers. The main goal is to define an HHT-related miRNAs signature. Particular attention has been paid on miRNAs-genotype and miRNAs-phenotype correlations. Here we present the preliminary results of this study. Methods: We performed a circulating miRNAs profiling in 15 subjects: 5 HHT1, 5 HHT2 Patients, and 5 controls, age and gender matched. miRNAs profile was analysed by qPCR, using serum/plasma microRNA PCR Panel (I + II), V4.M (Exiqon). Each panel contains 752 LNA™ primer sets of human miRNAs, including different controls. Statistical analyses were performed using parametric and non-parametric methods. miRNAs with a p value\0.05 were considered statistically significant and underwent enrichment analysis. Results: The overall result was the detection of 18 deregulated miRNAs. We observed differences between: HHT Patients versus controls; either HHT1 or HHT2 versus controls; HHT1 versus HHT2 Patients and also comparing Patients’ subgroups showing different clinical features. The enrichment analysis identified the top predicted target genes and the related pathways. Among these, we highlighted different pathways already described in association with HHT or angiogenesis. Conclusions: We obtained a preliminary “HHT signature” for circulating miRNAs, underlying, for the first time, differences between the two disease subtypes and a more peculiar miRNAs profile in HHT2. We also described miRNA-PAVMs (Pulmonary Arteriovenous Malformations) correlations. Confirmation of these results in a larger cohort of patients is therefore mandatory, and Patients enrolment for the second step of this study is ongoing