Differential Expression of Circulating Plasma miRNA-370 and miRNA-10a from Patients with Hereditary Hemorrhagic Telangiectasia
Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant, vascular disorder that presents with telangiectases and arteriovenous malformations. HHT is a genetically heterogeneous disorder, involving mutations in endoglin (<i>ENG</i>; HHT1) and activin receptor-like kinase 1 (&...
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MDPI AG
2020-09-01
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| Series: | Journal of Clinical Medicine |
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| Online Access: | https://www.mdpi.com/2077-0383/9/9/2855 |
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| author | Lidia Ruiz-Llorente Virginia Albiñana Luisa M. Botella Carmelo Bernabeu |
| author_facet | Lidia Ruiz-Llorente Virginia Albiñana Luisa M. Botella Carmelo Bernabeu |
| author_sort | Lidia Ruiz-Llorente |
| collection | DOAJ |
| description | Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant, vascular disorder that presents with telangiectases and arteriovenous malformations. HHT is a genetically heterogeneous disorder, involving mutations in endoglin (<i>ENG</i>; HHT1) and activin receptor-like kinase 1 (<i>ACVRL1</i>/<i>ALK1</i>; HHT2) genes that account for over 85% of all HHT patients. The current diagnosis of HHT patients remains at the clinical level, but many suspected patients do not have a clear HHT diagnosis or do not show pathogenic mutations in HHT genes. This situation has prompted the search for biomarkers to help in the early diagnosis of the disease. We have analyzed the plasma levels in HHT patients of selected micro-RNAs (miRNAs), small single-stranded RNAs that regulate gene expression at the transcriptional level by interacting with specific RNA targets. A total of 16 HHT1 and 17 HHT2 plasma samples from clinically confirmed patients and 16 controls were analyzed in this study. Total RNA was purified from plasma, and three selected miRNAs (miRNA-10a, miRNA-214, and miRNA-370), related to the pathobiology of cardiovascular diseases and potentially targeting <i>ENG</i> or <i>ALK1</i>, were measured by quantitative polymerase chain reaction. Compared with controls, levels of miRNA-370, whose putative target is <i>ENG</i>, were significantly downregulated in HHT1, but not in HHT2, whereas the levels of miRNA-10a, whose putative target is <i>ALK1</i>, were significantly upregulated in HHT2, but not in HHT1. In addition, the levels of miRNA-214, potentially targeting <i>ENG</i> and <i>ALK1,</i> did not change in either HHT1 or HHT2 patients versus control samples. While further studies are warranted, these results suggest that dysregulated plasma levels of miRNA-370 or miRNA-10a could help to identify undiagnosed HHT1 or HHT2 patients, respectively. |
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| language | English |
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| spelling | doaj.art-71bfec42196043b4b0d5ac3d95b1e3592023-11-20T12:30:18ZengMDPI AGJournal of Clinical Medicine2077-03832020-09-0199285510.3390/jcm9092855Differential Expression of Circulating Plasma miRNA-370 and miRNA-10a from Patients with Hereditary Hemorrhagic TelangiectasiaLidia Ruiz-Llorente0Virginia Albiñana1Luisa M. Botella2Carmelo Bernabeu3Centro de Investigaciones Biológicas Margarita Salas, Consejo Superior de Investigaciones Científicas (CSIC) and Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), 28040 Madrid, SpainCentro de Investigaciones Biológicas Margarita Salas, Consejo Superior de Investigaciones Científicas (CSIC) and Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), 28040 Madrid, SpainCentro de Investigaciones Biológicas Margarita Salas, Consejo Superior de Investigaciones Científicas (CSIC) and Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), 28040 Madrid, SpainCentro de Investigaciones Biológicas Margarita Salas, Consejo Superior de Investigaciones Científicas (CSIC) and Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), 28040 Madrid, SpainHereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant, vascular disorder that presents with telangiectases and arteriovenous malformations. HHT is a genetically heterogeneous disorder, involving mutations in endoglin (<i>ENG</i>; HHT1) and activin receptor-like kinase 1 (<i>ACVRL1</i>/<i>ALK1</i>; HHT2) genes that account for over 85% of all HHT patients. The current diagnosis of HHT patients remains at the clinical level, but many suspected patients do not have a clear HHT diagnosis or do not show pathogenic mutations in HHT genes. This situation has prompted the search for biomarkers to help in the early diagnosis of the disease. We have analyzed the plasma levels in HHT patients of selected micro-RNAs (miRNAs), small single-stranded RNAs that regulate gene expression at the transcriptional level by interacting with specific RNA targets. A total of 16 HHT1 and 17 HHT2 plasma samples from clinically confirmed patients and 16 controls were analyzed in this study. Total RNA was purified from plasma, and three selected miRNAs (miRNA-10a, miRNA-214, and miRNA-370), related to the pathobiology of cardiovascular diseases and potentially targeting <i>ENG</i> or <i>ALK1</i>, were measured by quantitative polymerase chain reaction. Compared with controls, levels of miRNA-370, whose putative target is <i>ENG</i>, were significantly downregulated in HHT1, but not in HHT2, whereas the levels of miRNA-10a, whose putative target is <i>ALK1</i>, were significantly upregulated in HHT2, but not in HHT1. In addition, the levels of miRNA-214, potentially targeting <i>ENG</i> and <i>ALK1,</i> did not change in either HHT1 or HHT2 patients versus control samples. While further studies are warranted, these results suggest that dysregulated plasma levels of miRNA-370 or miRNA-10a could help to identify undiagnosed HHT1 or HHT2 patients, respectively.https://www.mdpi.com/2077-0383/9/9/2855microRNAbiomarkerhereditary hemorrhagic telangiectasia (HHT)plasmatelangiectasesarteriovenous malformations (AVMs) |
| spellingShingle | Lidia Ruiz-Llorente Virginia Albiñana Luisa M. Botella Carmelo Bernabeu Differential Expression of Circulating Plasma miRNA-370 and miRNA-10a from Patients with Hereditary Hemorrhagic Telangiectasia Journal of Clinical Medicine microRNA biomarker hereditary hemorrhagic telangiectasia (HHT) plasma telangiectases arteriovenous malformations (AVMs) |
| title | Differential Expression of Circulating Plasma miRNA-370 and miRNA-10a from Patients with Hereditary Hemorrhagic Telangiectasia |
| title_full | Differential Expression of Circulating Plasma miRNA-370 and miRNA-10a from Patients with Hereditary Hemorrhagic Telangiectasia |
| title_fullStr | Differential Expression of Circulating Plasma miRNA-370 and miRNA-10a from Patients with Hereditary Hemorrhagic Telangiectasia |
| title_full_unstemmed | Differential Expression of Circulating Plasma miRNA-370 and miRNA-10a from Patients with Hereditary Hemorrhagic Telangiectasia |
| title_short | Differential Expression of Circulating Plasma miRNA-370 and miRNA-10a from Patients with Hereditary Hemorrhagic Telangiectasia |
| title_sort | differential expression of circulating plasma mirna 370 and mirna 10a from patients with hereditary hemorrhagic telangiectasia |
| topic | microRNA biomarker hereditary hemorrhagic telangiectasia (HHT) plasma telangiectases arteriovenous malformations (AVMs) |
| url | https://www.mdpi.com/2077-0383/9/9/2855 |
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