{"doi":"10.1161/atvbaha.107.141200","title":"Dysregulated Bone Morphogenetic Protein Signaling in Monocrotaline-Induced Pulmonary Arterial Hypertension","abstract":"<jats:p>\n            <jats:bold>\n              <jats:italic>Background—</jats:italic>\n            </jats:bold>\n            Mutations in the\n            <jats:italic>bmpr2</jats:italic>\n            gene, encoding the type II bone morphogenetic protein (BMP) receptor, have been identified in patients with pulmonary arterial hypertension (PAH), implicating BMP signaling in PAH. The aim of this study was to assess BMP signaling and its physiological effects in a monocrotaline (MCT) model of PAH.\n          </jats:p>\n          <jats:p>\n            <jats:bold>\n              <jats:italic>Methods and Results—</jats:italic>\n            </jats:bold>\n            Expression of BMP receptors Ib and II, and Smads 4, 5, 6, and 8, was downregulated in lungs but not kidneys of MCT-treated rats. Smad1 phosphorylation and expression of BMP/Smad target genes\n            <jats:italic>id1</jats:italic>\n            and\n            <jats:italic>id3</jats:italic>\n            was also reduced, although ERK1/2 and p38\n            <jats:sup>MAPK</jats:sup>\n            phosphorylation remained unaffected. BMP receptor and Smad expression, Smad1 phosphorylation, and induction of the BMP/Smad-responsive element of the\n            <jats:italic>id1</jats:italic>\n            promoter were reduced in pulmonary artery smooth muscle cells (PASMCs) from MCT-treated rats. As a consequence of impaired BMP/Smad signaling, PASMCs from MCT-treated rats were resistant to apoptosis induced by BMP-4 and BMP-7, and were also resistant to BMP-4 antagonism of proliferation induced by platelet-derived growth factor.\n          </jats:p>\n          <jats:p>\n            <jats:bold>\n              <jats:italic>Conclusion—</jats:italic>\n            </jats:bold>\n            BMP signaling and BMP-regulated physiological phenomena are perturbed in MCT-treated rats, lending solid support to the proposed roles for BMP signaling in the pathogenesis of human PAH.\n          </jats:p>","journal":"Arteriosclerosis, Thrombosis, and Vascular Biology","year":2007,"id":35802,"datarank":6.995478582203305,"base_score":4.962844630259907,"endowment":4.962844630259907,"self_citation_contribution":0.7444266945389861,"citation_network_contribution":6.251051887664319,"self_endowment_contribution":0.7444266945389861,"citer_contribution":6.251051887664319,"corpus_percentile":null,"corpus_rank":null,"citation_count":142,"citer_count":124,"citers_with_citation_signal":117,"citers_with_endowment":117,"datacite_reuse_total":2,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":182643,"name":"Bozena Nejman","orcid":null,"position":1,"is_corresponding":false},{"id":143546,"name":"Grazyna Kwapiszewska","orcid":null,"position":2,"is_corresponding":false},{"id":182644,"name":"Matthias Hecker","orcid":null,"position":3,"is_corresponding":false},{"id":182645,"name":"Anka Zakrzewicz","orcid":null,"position":4,"is_corresponding":false},{"id":182646,"name":"Fotini M. Kouri","orcid":null,"position":5,"is_corresponding":false},{"id":182647,"name":"Dorothea M. Peters","orcid":null,"position":6,"is_corresponding":false},{"id":153712,"name":"Rio Dumitrascu","orcid":null,"position":7,"is_corresponding":false},{"id":89032,"name":"Werner Seeger","orcid":"0000-0003-1946-0894","position":8,"is_corresponding":false},{"id":182648,"name":"Petra Knaus","orcid":null,"position":9,"is_corresponding":false},{"id":154646,"name":"Ralph T. Schermuly","orcid":null,"position":10,"is_corresponding":false},{"id":572,"name":"Oliver Eickelberg","orcid":"0000-0001-7170-0360","position":11,"is_corresponding":false},{"id":64800,"name":"Rory E. Morty","orcid":"0000-0003-0833-9749","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"base_score":4.962844630259907,"endowment":4.962844630259907,"datacite_reuse_total":2,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"17347486","pmcid":null,"openalex_id":"https://openalex.org/W1994324715","authors":[],"funders":[],"total_grants":0,"fwci":9.2676,"citation_percentile":0.9821516,"influential_citations":5,"citation_trend":[{"year":2012,"count":5},{"year":2013,"count":13},{"year":2014,"count":16},{"year":2015,"count":6},{"year":2016,"count":3},{"year":2017,"count":8},{"year":2018,"count":8},{"year":2019,"count":4},{"year":2020,"count":4},{"year":2021,"count":7},{"year":2022,"count":5},{"year":2023,"count":4},{"year":2024,"count":3},{"year":2025,"count":6},{"year":2026,"count":1}],"oa_status":"closed","license":null,"oa_locations":[{"url":"https://www.ahajournals.org/doi/full/10.1161/ATVBAHA.107.141200","host_type":"publisher"},{"url":"https://doi.org/10.1161/atvbaha.107.141200","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/17347486","host_type":"repository"}],"fields_of_study":["Pulmonary Hypertension Research and Treatments","Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis","TGF-β signaling in diseases","Medicine","Biology","Animals","Apoptosis","Bone Morphogenetic Protein Receptors, Type I","Bone Morphogenetic Protein Receptors, Type II","Cell Proliferation","Disease Models, Animal","Disease Progression","Down-Regulation","Hypertension, Pulmonary","Immunoblotting","Immunohistochemistry","Male","Monocrotaline","Polymerase Chain Reaction","Pulmonary Artery","RNA","Rats","Rats, Sprague-Dawley","Signal Transduction","Smad4 Protein","Smad5 Protein","Smad6 Protein","Smad8 Protein"],"mesh_terms":["Animals","Disease Models, Animal","Hypertension, Pulmonary","Immunohistochemistry","Male","Pulmonary Artery","RNA","Immunoblotting","Signal Transduction","Down-Regulation","Polymerase Chain Reaction","Monocrotaline","Rats, Sprague-Dawley","Apoptosis","Disease Progression","Cell Proliferation","Rats","Smad4 Protein","Smad5 Protein","Smad8 Protein","Smad6 Protein","Bone Morphogenetic Protein Receptors, Type I","Bone Morphogenetic Protein Receptors, Type II"],"keywords":["BMPR2","SMAD","Bone morphogenetic protein","Bone morphogenetic protein receptor","Phosphorylation","Signal transduction","Bone morphogenetic protein 7","Bone morphogenetic protein 2","Internal medicine","Endocrinology","Cancer research","Medicine","Biology","Cell biology","Gene","Biochemistry"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[{"doi":"10.6084/m9.figshare.19561209.v1","title":"Additional file 1 of CRISPR-mediated Bmpr2 point mutation exacerbates late pulmonary vasculopathy and reduces survival in rats with experimental pulmonary hypertension","publisher":"figshare","resource_type":"JournalArticle"},{"doi":"10.6084/m9.figshare.19561209","title":"Additional file 1 of CRISPR-mediated Bmpr2 point mutation exacerbates late pulmonary vasculopathy and reduces survival in rats with experimental pulmonary hypertension","publisher":"figshare","resource_type":"JournalArticle"}],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-06-10T09:28:54.269830Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}