Decreased Levels of MicroRNAs-28-5p, -361-3p and Increased Insulin-Like Growth Factor 1 mRNA Levels in Mononuclear Cells from Hereditary Hemorrhagic Telangiectasia Patients.

Hereditary hemorrhagic telangiectasia (HHT) is a rare vascular disorder inherited in an autosomal dominant manner. Patients with HHT can develop vascular dysplasias called telangiectasias and arteriovenous malformations (AVMs). Our objective was to profile and characterize microRNAs (miRs), short-noncoding RNAs that regulate gene expression post-transcriptionally, in HHT patient derived peripheral blood mononuclear cells (PBMCs). PBMCs, comprised mostly of lymphocytes and monocytes, have been reported to be dysfunctional in HHT. A total of 40 clinically confirmed HHT patients and 22 controls were enrolled in this study. PBMCs were isolated from 16 ml of peripheral blood and purified for total RNA. MiR expression profiling was conducted with a human miR array analysis. Select dysregulated miRs and miR targets were validated with RT-qPCR. Of the 377 miRs screened, 41 dysregulated miRs were identified. MiR-28-5p and miR-361-3p, known to target insulin-like growth factor 1 (IGF1), a potent angiogenic growth factor, were found to be significantly downregulated in patients. Consequently, IGF1 mRNA levels were found to be significantly elevated. Our research successfully identified miR dysregulation and elevated IGF1 mRNA levels in HHT PBMCs. This novel discovery represents a potential pathogenic mechanism that could be targeted to alleviate clinical manifestations of HHT.