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Allen Frontiers Group Distinguished Investigator Award"},{"name":"Forschungsgemeinschaft","award":["SFB1213 Project A11N"],"award-info":[{"award-number":["SFB1213 Project A11N"]}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["J Histochem Cytochem."],"published-print":{"date-parts":[[2025,4]]},"abstract":"<jats:p>Pulmonary arterial hypertension (PAH) is a lethal condition where expansion of the vascular extracellular matrix contributes to increased pulmonary vascular resistance. Versican, a chondroitin sulfate proteoglycan, is known to accumulate in vascular lesions of PAH and hyaluronan and tenascin-C, binding partners of versican, are elevated in PAH. The specific distribution and localization of versican isoforms, their cleavage products, and binding partners in vascular lesions of PAH had not been studied previously. Versican has five distinct isoforms, V0\u2013V4, identified by the arrangement of its chondroitin-sulfate attachment regions, GAG\u03b1 and GAG\u03b2. Here, tissue from idiopathic PAH was imaged with synchrotron-based phase-contrast micro-CT and analyzed by histology, immunohistochemistry, and in situ hybridization. Plasma concentration of versican in PAH patients and controls was measured using ELISA. GAG\u03b1- and GAG\u03b2-containing isoforms were identified in pulmonary arteriopathy of all patients. However, immunohistochemical staining of N-terminal G1 domain (versican G1) and C-terminal G3 domain (versican G3) using specific antibodies did not consistently co-localize. Tenascin-C was occasionally found in neointima, but also in thin-walled collateral vessels. Hyaluronan accumulated in the neointima, co-localizing with both versican G3 and the neoepitope DPEAAE. DPEAAE did not co-localize with the corresponding neoepitope of the C-terminal fragment generated by cleavage, possibly indicating motility of fragments. Patient plasma had a higher concentration of versican G3-containing fragments, compared to controls. The distribution of versican isoforms, cleavage products, and binding partners demonstrated here warrants further investigation of their functional roles in PAH, versican G3 was reinforced as a potential biomarker for PAH.<\/jats:p>","DOI":"10.1369\/00221554251331271","type":"journal-article","created":{"date-parts":[[2025,4,12]],"date-time":"2025-04-12T01:17:21Z","timestamp":1744420641000},"page":"129-145","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["Localization, Proteolytic Processing, and Binding Partners of Versican Isoforms in Vascular Lesions of Pulmonary Arterial Hypertension"],"prefix":"10.1369","volume":"73","author":[{"given":"Christian","family":"West\u00f6\u00f6","sequence":"first","affiliation":[{"name":"Department of Experimental Medical Science, Lund University, Lund, Sweden"},{"name":"Wallenberg Centre for Molecular Medicine, Lund University, Lund, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4981-3646","authenticated-orcid":false,"given":"Ayse Ceren","family":"Mutgan","sequence":"additional","affiliation":[{"name":"Department of Experimental Medical Science, Lund University, Lund, Sweden"},{"name":"Wallenberg Centre for Molecular Medicine, Lund University, Lund, Sweden"},{"name":"Lung Research Cluster, Otto Loewi Research Center, Medical University of Graz, Graz, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4726-0697","authenticated-orcid":false,"given":"Oscar","family":"van der Have","sequence":"additional","affiliation":[{"name":"Department of Experimental Medical Science, Lund University, Lund, Sweden"},{"name":"Wallenberg Centre for Molecular Medicine, Lund University, Lund, Sweden"},{"name":"Children\u2019s Heart Centre, Sk\u00e5ne University Hospital, Lund, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1891-3652","authenticated-orcid":false,"given":"Timothy J.","family":"Mead","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, Cleveland Clinic Lerner Research Institute, Cleveland, OH"},{"name":"Department of Pediatrics, School of Medicine, Case Western Reserve University, Cleveland, OH"},{"name":"University Hospitals Rainbow Babies &amp; Children\u2019s Hospital, Cleveland, OH"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7086-6262","authenticated-orcid":false,"given":"Salaheldin","family":"Ahmed","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences Lund, Cardiology, Lund University, Lund, Sweden"},{"name":"The Hemodynamic Lab, The Section for Heart Failure and Valvular Disease, VO. Heart and Lung Medicine, Department of Clinical Science Lund, Cardiology, Sk\u00e5ne University Hospital, Lund, Sweden"},{"name":"Department of Education and Research, Helsingborg Hospital, Helsingborg, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elna","family":"Lampei","sequence":"additional","affiliation":[{"name":"Department of Experimental Medical Science, Lund University, Lund, Sweden"},{"name":"Wallenberg Centre for Molecular Medicine, Lund University, Lund, Sweden"},{"name":"Children\u2019s Heart Centre, Sk\u00e5ne University Hospital, Lund, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5220-664X","authenticated-orcid":false,"given":"Christopher D.","family":"Koch","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, Cleveland Clinic Lerner Research Institute, Cleveland, OH"},{"name":"Department of Pathology, Sanford School of Medicine, University of South Dakota, Sioux Falls, SD"},{"name":"Sanford Laboratories, Sanford Health, Sioux Falls, SD"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christian","family":"Norvik","sequence":"additional","affiliation":[{"name":"Department of Experimental Medical Science, Lund University, Lund, Sweden"},{"name":"Wallenberg Centre for Molecular Medicine, Lund University, Lund, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anders","family":"Aspberg","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences Lund, Rheumatology and Molecular Skeletal Biology, Lund University, Lund, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9109-7175","authenticated-orcid":false,"given":"Martin","family":"Bech","sequence":"additional","affiliation":[{"name":"Medical Radiation Physics, Department of Clinical Sciences, Lund University, Lund, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2929-4247","authenticated-orcid":false,"given":"Niccol\u00f2","family":"Peruzzi","sequence":"additional","affiliation":[{"name":"Department of Experimental Medical Science, Lund University, Lund, Sweden"},{"name":"Wallenberg Centre for Molecular Medicine, Lund University, Lund, Sweden"},{"name":"Medical Radiation Physics, Department of Clinical Sciences, Lund University, Lund, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7402-138X","authenticated-orcid":false,"given":"Hans","family":"Brunnstr\u00f6m","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences Lund, Division of Pathology, Lund University, Lund, Sweden"},{"name":"Department of Genetics and Pathology, Division of Laboratory Medicine, Region Sk\u00e5ne, Lund, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0518-9079","authenticated-orcid":false,"given":"Grazyna","family":"Kwapiszewska","sequence":"additional","affiliation":[{"name":"Lung Research Cluster, Otto Loewi Research Center, Medical University of Graz, Graz, Austria"},{"name":"Institute for Lung Health, German Center for Lung Research (DZL), Cardio Pulmonary Institute, Giessen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"G\u00f6ran","family":"R\u00e5degran","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences Lund, Cardiology, Lund University, Lund, Sweden"},{"name":"The Hemodynamic Lab, The Section for Heart Failure and Valvular Disease, VO. 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Developmental Studies Hybridoma Bank (DSHB) Antibody Registry ID:AB_528503."},{"key":"e_1_3_4_48_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-17613-6"},{"key":"e_1_3_4_49_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.R109.052340"},{"key":"e_1_3_4_50_2","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2016-3527"},{"key":"e_1_3_4_51_2","doi-asserted-by":"publisher","DOI":"10.1042\/bj1990297"},{"key":"e_1_3_4_52_2","article-title":"Expression of the extracellular matrix proteoglycan, versican, in human skin","volume":"78","author":"Zimmermann DR","year":"1994","unstructured":"Zimmermann DR, Dours-Zimmermann MT, Schubert M, Bruckner-Tuderman L, Heitz PU. Expression of the extracellular matrix proteoglycan, versican, in human skin. 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