{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T17:55:32Z","timestamp":1790445332158,"version":"4.1.0"},"reference-count":57,"publisher":"Oxford University Press (OUP)","issue":"12","license":[{"start":{"date-parts":[[2024,7,18]],"date-time":"2024-07-18T00:00:00Z","timestamp":1721260800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,10,14]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Pulmonary vascular and right ventricular (RV) remodelling processes are important for development and progression of pulmonary hypertension (PH). The current study analysed the functional role of the extra domain A-containing fibronectin (ED-A+ Fn) for the development of PH by comparing ED-A+ Fn knockout (KO) and wild-type (WT) mice as well as the effects of an antibody-based therapeutic approach in a model of monocrotaline (MCT)-induced PH, which will be validated in a model of Sugen 5416\/hypoxia-induced PH.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>PH was induced using MCT (PH mice). Sixty-nine mice were divided into the following groups: sham-treated controls (WT: n = 7; KO: n = 7), PH mice without specific treatment (WT: n = 12; KO: n = 10), PH mice treated with a dual endothelin receptor antagonist (macitentan; WT: n = 6; KO: n = 11), WT PH mice treated with the F8 antibody, specifically recognizing ED-A+ Fn, (n = 8), and WT PH mice treated with an antibody of irrelevant antigen specificity (KSF, n = 8). Compared to controls, WT_PH mice showed a significant elevation of the RV systolic pressure (P = 0.04) and RV functional impairment including increased basal RV (P = 0.016) diameter or tricuspid annular plane systolic excursion (P = 0.008). In contrast, KO PH did not show such effects compared to controls (P = n.s.). In WT_PH mice treated with F8, haemodynamic and echocardiographic parameters were significantly improved compared to untreated WT_PH mice or those treated with the KSF antibody (P &amp;lt; 0.05). On the microscopic level, KO_PH mice showed significantly less tissue damage compared to the WT_PH mice (P = 0.008). Furthermore, lung tissue damage could significantly be reduced after F8 treatment (P = 0.04). Additionally, these findings could be verified in the Sugen 5416\/hypoxia mouse model, in which F8 significantly improved echocardiographic, haemodynamic, and histologic parameters.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>ED-A+ Fn is of crucial importance for PH pathogenesis representing a promising therapeutic target in PH. We here show a novel therapeutic approach using antibody-mediated functional blockade of ED-A+ Fn capable of attenuating and partially reversing PH-associated tissue remodelling.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/cvr\/cvae146","type":"journal-article","created":{"date-parts":[[2024,7,17]],"date-time":"2024-07-17T01:35:03Z","timestamp":1721180103000},"page":"1485-1497","source":"Crossref","is-referenced-by-count":3,"title":["Extra domain A-containing fibronectin in pulmonary hypertension and treatment effects of a function-blocking antibody"],"prefix":"10.1093","volume":"120","author":[{"given":"Isabell","family":"Singerer","sequence":"first","affiliation":[{"name":"Department of Internal Medicine I, University Hospital Jena , Am Klinikum 1, 07747 Jena ,","place":["Germany"]},{"name":"Department of Cardiology, Angiology and Intensive Care Medicine, Cardiovascular Center Rotenburg, Klinikum Hersfeld-Rotenburg, Heinz-Meise-Str. 100, 36199 Rotenburg an der Fulda ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Tempel","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine I, University Hospital Jena , Am Klinikum 1, 07747 Jena ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katja","family":"Gruen","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine I, University Hospital Jena , Am Klinikum 1, 07747 Jena ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Judith","family":"Hei\u00df","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine I, University Hospital Jena , Am Klinikum 1, 07747 Jena ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clara","family":"Gutte","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine I, University Hospital Jena , Am Klinikum 1, 07747 Jena ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mattia","family":"Matasci","sequence":"additional","affiliation":[{"name":"Philochem AG , Otelfingen ,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Schrepper","sequence":"additional","affiliation":[{"name":"Department of Cardiothoracic Surgery, University Hospital Jena , Jena ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reinhard","family":"Bauer","sequence":"additional","affiliation":[{"name":"Center for Molecular Biomedicine, Institute of Molecular Cell Biology, University Hospital Jena , Jena ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Berndt","sequence":"additional","affiliation":[{"name":"Section Pathology, Institute of Legal Medicine, University Hospital Jena , Jena ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Jung","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Pulmonology, and Vascular Medicine, Medical Faculty, Heinrich-Heine University D\u00fcsseldorf , D\u00fcsseldorf ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P Christian","family":"Schulze","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine I, University Hospital Jena , Am Klinikum 1, 07747 Jena ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dario","family":"Neri","sequence":"additional","affiliation":[{"name":"Philochem AG , Otelfingen ,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcus","family":"Franz","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine I, University Hospital Jena , Am Klinikum 1, 07747 Jena ,","place":["Germany"]},{"name":"Department of Cardiology, Angiology and Intensive Care Medicine, Cardiovascular Center Rotenburg, Klinikum Hersfeld-Rotenburg , Heinz-Meise-Str. 100, 36199 Rotenburg an der Fulda ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2024,7,18]]},"reference":[{"key":"2024101413505166400_cvae146-B1","doi-asserted-by":"crossref","first-page":"3618","DOI":"10.1093\/eurheartj\/ehac237","article-title":"2022 ESC\/ERS guidelines for the diagnosis and treatment of pulmonary hypertension: developed by the task force for the diagnosis and treatment of pulmonary hypertension of the European Society of Cardiology (ESC) and the European Respiratory Society (ERS). 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