{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T05:44:54Z","timestamp":1791870294533,"version":"4.3.4"},"reference-count":50,"publisher":"Oxford University Press (OUP)","issue":"11","license":[{"start":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T00:00:00Z","timestamp":1753833600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000274","name":"British Heart Foundation","doi-asserted-by":"publisher","award":["PG\/22\/10916"],"award-info":[{"award-number":["PG\/22\/10916"]}],"id":[{"id":"10.13039\/501100000274","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000294","name":"Medical Research Scotland PhD studentship","doi-asserted-by":"publisher","award":["PHD-50197-2020"],"award-info":[{"award-number":["PHD-50197-2020"]}],"id":[{"id":"10.13039\/501100000294","id-type":"DOI","asserted-by":"publisher"}]},{"name":"BHF Clinical Research Training Fellowship","award":["FS\/19\/15\/34155"],"award-info":[{"award-number":["FS\/19\/15\/34155"]}]},{"name":"Edinburgh Scientific Academic Track"},{"name":"REA3 Institutional Award","award":["RE\/18\/5\/34216"],"award-info":[{"award-number":["RE\/18\/5\/34216"]}]},{"name":"AtheroNET COST Action","award":["CA21153"],"award-info":[{"award-number":["CA21153"]}]},{"name":"EU-COST"},{"DOI":"10.13039\/501100000921","name":"European Cooperation in Science and Technology","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000921","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,9,29]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Aims<\/jats:title>\n                  <jats:p>Vascular calcification is the abnormal deposition of calcium phosphates within blood vessels. This condition is significantly associated with the development of cardiovascular disease, yet the underlying mechanisms remain largely unknown. MicroRNAs (miRNAs) may be crucial in initiating vascular calcification by regulating a network of specific cellular targets. In this study, we explored for the first time the potential role of microRNA-26b (miR-26b) in vascular calcification.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods and results<\/jats:title>\n                  <jats:p>Using micro-positron emission tomography and computed tomography (micro-PET\/CT) imaging with 18F\u2013sodium fluoride, we measured aortic calcification in miR-26b knockout mice (miR-26bKO). We conducted bulk RNA sequencing (RNA-seq), single-cell RNA sequencing, and network analysis to identify cell-specific targets and the cellular complexity contributing to the observed phenotype. Additionally, we examined aortic tissues from patients with aortic aneurysm or valvular-related aortopathy to determine how the expression levels of miR-26b and its targets correlate with calcification. Our findings revealed that miR-26b is downregulated in the aortic tissues of patients with aortic calcification, whereas miR-26b expression negatively correlates with calcification levels. Similarly, miR-26bKO mice developed spontaneous age-related aortic microcalcifications. Combining single-cell transcriptomics with network analyses, we identified and mapped cell-type specific targets of miR-26b and regulatory pathways. Furthermore, we validated the cell-specific expression of Smad1 in smooth muscle cells (SMCs) and characterized the cell\u2013cell communication between aortic cells, exposing the bone morphogenetic protein (BMP) pathway. The development of microcalcification was attributed to Bmp4 released from fibroblasts (FBLs), leading to Smad1 phosphorylation and calcium accumulation in SMCs of miR-26bKO mice. We found that aortic microcalcification could be pharmacologically reversed by disrupting cellular communication. Lastly, we demonstrated an inverse correlation between miR-26b and SMAD1 levels in calcified aortic tissues.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>The deficiency of miR-26b is crucial for initiating and promoting aortic calcification, revealing new therapeutic targets for aortic disease.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/cvr\/cvaf117","type":"journal-article","created":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T17:04:31Z","timestamp":1753895071000},"page":"1778-1792","source":"Crossref","is-referenced-by-count":6,"title":["The loss of microRNA-26b promotes aortic calcification through the regulation of cell-specific target genes"],"prefix":"10.1093","volume":"121","author":[{"given":"Diana","family":"Luna Buitrago","sequence":"first","affiliation":[{"name":"University\/BHF Centre for Cardiovascular Science, The Queen\u2019s Medical Research Institute, The University of Edinburgh , 47 Little France Crescent, Edinburgh EH16 4TJ ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva","family":"Jover","sequence":"additional","affiliation":[{"name":"Cardiovascular Translational Research, Navarrabiomed (Fundaci\u00f3n Miguel Servet), Instituto de Investigaci\u00f3n Sanitaria de Navarra (IdiSNA), Hospital Universitario de Navarra (HUN), Universidad P\u00fablica de Navarra (UPNA) , Pamplona ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eleonora","family":"Mameli","sequence":"additional","affiliation":[{"name":"University\/BHF Centre for Cardiovascular Science, The Queen\u2019s Medical Research Institute, The University of Edinburgh , 47 Little France Crescent, Edinburgh EH16 4TJ ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Mellis","sequence":"additional","affiliation":[{"name":"University\/BHF Centre for Cardiovascular Science, The Queen\u2019s Medical Research Institute, The University of Edinburgh , 47 Little France Crescent, Edinburgh EH16 4TJ ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4661-8773","authenticated-orcid":false,"given":"Ryszard","family":"Nosalski","sequence":"additional","affiliation":[{"name":"University\/BHF Centre for Cardiovascular Science, The Queen\u2019s Medical Research Institute, The University of Edinburgh , 47 Little France Crescent, Edinburgh EH16 4TJ ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Charlton","sequence":"additional","affiliation":[{"name":"School of Engineering, King\u2019s Buildings, The University of Edinburgh , Edinburgh ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosa","family":"Bauza Sanso","sequence":"additional","affiliation":[{"name":"University\/BHF Centre for Cardiovascular Science, The Queen\u2019s Medical Research Institute, The University of Edinburgh , 47 Little France Crescent, Edinburgh EH16 4TJ ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hywel","family":"Dunn-Davies","sequence":"additional","affiliation":[{"name":"MRC Human Genetics Unit, MRC Institute of Genetics and Cancer, The University of Edinburgh , Edinburgh ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark G","family":"MacAskill","sequence":"additional","affiliation":[{"name":"University\/BHF Centre for Cardiovascular Science, The Queen\u2019s Medical Research Institute, The University of Edinburgh , 47 Little France Crescent, Edinburgh EH16 4TJ ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adriana A S","family":"Tavares","sequence":"additional","affiliation":[{"name":"University\/BHF Centre for Cardiovascular Science, The Queen\u2019s Medical Research Institute, The University of Edinburgh , 47 Little France Crescent, Edinburgh EH16 4TJ ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander J","family":"Fletcher","sequence":"additional","affiliation":[{"name":"University\/BHF Centre for Cardiovascular Science, The Queen\u2019s Medical Research Institute, The University of Edinburgh , 47 Little France Crescent, Edinburgh EH16 4TJ ,","place":["UK"]},{"name":"School of Cardiovascular and Metabolic Health, BHF Centre of Research Excellence, The University of Glasgow , Glasgow ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Nash","sequence":"additional","affiliation":[{"name":"University\/BHF Centre for Cardiovascular Science, The Queen\u2019s Medical Research Institute, The University of Edinburgh , 47 Little France Crescent, Edinburgh EH16 4TJ ,","place":["UK"]},{"name":"School of Cardiovascular and Metabolic Health, BHF Centre of Research Excellence, The University of Glasgow , Glasgow ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalia","family":"L\u00f3pez-Andr\u00e9s","sequence":"additional","affiliation":[{"name":"Cardiovascular Translational Research, Navarrabiomed (Fundaci\u00f3n Miguel Servet), Instituto de Investigaci\u00f3n Sanitaria de Navarra (IdiSNA), Hospital Universitario de Navarra (HUN), Universidad P\u00fablica de Navarra (UPNA) , Pamplona ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc R","family":"Dweck","sequence":"additional","affiliation":[{"name":"University\/BHF Centre for Cardiovascular Science, The Queen\u2019s Medical Research Institute, The University of Edinburgh , 47 Little France Crescent, Edinburgh EH16 4TJ ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick W F","family":"Hadoke","sequence":"additional","affiliation":[{"name":"University\/BHF Centre for Cardiovascular Science, The Queen\u2019s Medical Research Institute, The University of Edinburgh , 47 Little France Crescent, Edinburgh EH16 4TJ ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Derek S","family":"Gilchrist","sequence":"additional","affiliation":[{"name":"School of Infection and Immunity, College of Medical Veterinary and Life Sciences , The University of Glasgow, Glasgow ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brad D","family":"Wagner","sequence":"additional","affiliation":[{"name":"Department of Biology and Centre for Visual Sciences, Miami University , Oxford, OH ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael L","family":"Robinson","sequence":"additional","affiliation":[{"name":"Department of Biology and Centre for Visual Sciences, Miami University , Oxford, OH ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew H","family":"Baker","sequence":"additional","affiliation":[{"name":"University\/BHF Centre for Cardiovascular Science, The Queen\u2019s Medical Research Institute, The University of Edinburgh , 47 Little France Crescent, Edinburgh EH16 4TJ ,","place":["UK"]},{"name":"Department of Pathology, CARIM, Maastricht University , Maastricht ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David E","family":"Newby","sequence":"additional","affiliation":[{"name":"University\/BHF Centre for Cardiovascular Science, The Queen\u2019s Medical Research Institute, The University of Edinburgh , 47 Little France Crescent, Edinburgh EH16 4TJ ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6852-8982","authenticated-orcid":false,"given":"Tijana","family":"Miti\u0107","sequence":"additional","affiliation":[{"name":"University\/BHF Centre for Cardiovascular Science, The Queen\u2019s Medical Research 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