{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,6]],"date-time":"2025-11-06T20:14:50Z","timestamp":1762460090569,"version":"build-2065373602"},"reference-count":76,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2022,4,9]],"date-time":"2022-04-09T00:00:00Z","timestamp":1649462400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["U54 NS065705"],"award-info":[{"award-number":["U54 NS065705"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Background. Hereditary hemorrhagic telangiectasia (HHT) is a rare, autosomal dominant genetic disorder characterized by life-threatening vascular dysplasia. Myeloid angiogenic cells (MACs), alternatively called early endothelial progenitor cells or circulating angiogenic cells, do not directly incorporate into developing blood vessels, but augment angiogenesis in a paracrine manner. MAC dysfunction has been reported in HHT. MicroRNAs (miRNAs) regulate cellular function by modulating gene expression post-transcriptionally. To date, the role of miRNAs in HHT MAC dysfunction has not been documented. Objective. The goal of this study was to comparatively profile miRNAs in HHT patient and control MACs to identify dysregulated miRNAs that may be responsible for the observed MAC dysfunction in HHT. Methodology\/Results. Twenty-three dysregulated miRNAs (twenty-one upregulated and two downregulated) in HHT MACs were identified with a TaqMan miRNA microarray. Pathway enrichment analysis showed that the dysregulated miRNAs were significantly enriched in pathways involved in HHT pathogenesis, such as the transforming growth factor \u03b2 (TGF\u03b2), phosphatidylinositol 3-kinase\/protein kinase B (PI3K\/AKT), and Hippo signalling pathways. Furthermore, miR-132-3p was determined to be significantly reduced in HHT MACs compared with controls by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Bioinformatic analysis revealed that miR-132-3p is significantly enriched in the TGF\u03b2 and PI3K\/AKT signalling pathways, targeting SMAD4, an effector of the TGF\u03b2 signalling pathway and RASA1, a negative regulator of the PI3K\/AKT signalling pathway, respectively. Conclusion. MiRNA dysregulation, specifically reduced expression of miR-132-3p, in HHT MACs was identified. The dysregulated miRNAs are significantly enriched in the TGF\u03b2, PI3K\/AKT, and Hippo signalling pathways. These data suggest that alteration in miRNA expression may impair these pathways and contribute to MAC dysfunction in HHT.<\/jats:p>","DOI":"10.3390\/genes13040665","type":"journal-article","created":{"date-parts":[[2022,4,9]],"date-time":"2022-04-09T05:13:08Z","timestamp":1649481188000},"page":"665","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["MicroRNA-132-3p, Downregulated in Myeloid Angiogenic Cells from Hereditary Hemorrhagic Telangiectasia Patients, Is Enriched in the TGF\u03b2 and PI3K\/AKT Signalling Pathways"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7299-8891","authenticated-orcid":false,"given":"Anthony","family":"Cannavicci","sequence":"first","affiliation":[{"name":"Institute of Medical Science, Cardiovascular Sciences Specialization Program, University of Toronto, Toronto, ON M5S 1A8, Canada"},{"name":"Keenan Research Center for Biomedical Science, Division of Cardiology, St. Michael\u2019s Hospital, Unity Health Toronto, Toronto, ON M5B 1T8, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qiuwang","family":"Zhang","sequence":"additional","affiliation":[{"name":"Keenan Research Center for Biomedical Science, Division of Cardiology, St. Michael\u2019s Hospital, Unity Health Toronto, Toronto, ON M5B 1T8, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marie E.","family":"Faughnan","sequence":"additional","affiliation":[{"name":"Institute of Medical Science, Cardiovascular Sciences Specialization Program, University of Toronto, Toronto, ON M5S 1A8, Canada"},{"name":"Toronto HHT Centre, Li Ka Shing Knowledge Institute, St. Michael\u2019s Hospital, Unity Health Toronto, Toronto, ON M5B 1T8, Canada"},{"name":"Department of Medicine, Division of Respirology, University of Toronto, Toronto, ON M5S 3H2, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael J. B.","family":"Kutryk","sequence":"additional","affiliation":[{"name":"Institute of Medical Science, Cardiovascular Sciences Specialization Program, University of Toronto, Toronto, ON M5S 1A8, Canada"},{"name":"Keenan Research Center for Biomedical Science, Division of Cardiology, St. Michael\u2019s Hospital, Unity Health Toronto, Toronto, ON M5B 1T8, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,4,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"860","DOI":"10.1038\/ejhg.2009.35","article-title":"Hereditary Haemorrhagic Telangiectasia: A Clinical and Scientific Review","volume":"17","author":"Govani","year":"2009","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"918","DOI":"10.1056\/NEJM199510053331407","article-title":"Hereditary Hemorrhagic Telangiectasia","volume":"333","author":"Guttmacher","year":"1995","journal-title":"N. Engl. J. 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