{"doi":"10.17615/etjk-0n67","title":"A Monoclonal Antibody Against  V 3 Integrin Inhibits Development of Atherosclerotic Lesions in Diabetic Pigs","abstract":"Atherosclerotic lesions develop and progress more rapidly in diabetic patients than in nondiabetic individuals. This may be caused by accelerated lesion formation in the high-glucose environment of diabetes. Smooth muscle cells (SMCs) cultured in high glucose are more responsive to growth factors such as insulin-like growth factor–1 (IGF-1). This enhanced response to IGF-1 is due in part to increased activation of the αVβ3 integrin. We tested whether αVβ3 integrin activation was increased in diabetic animals and whether an antibody to β3 would inhibit IGF-1 action and development of atherosclerosis. Eight male pigs were made diabetic with streptozotocin and fed a high-fat diet. A F(ab)2 antibody fragment directed at β3 was infused into one femoral artery, whereas the other artery received control F(ab)2 for 3.5 months. There was a 65 ± 8% reduction in atherosclerotic lesion area in the arteries treated with F(ab)2 antibody to β3. Phosphorylation of β3 was reduced by 75 ± 18% in vessels treated with the antibody. Shc and mitogen-activated protein kinase phosphorylation, which are required for IGF-1–stimulated SMC proliferation, were also significantly reduced. We conclude that activation of IGF-1 receptor and αVβ3-linked signaling pathways accelerates atherosclerosis in diabetes and that administration of an antibody to β3 to diabetic pigs inhibits αVβ3 activation, IGF-1–stimulated signaling, and atherosclerotic lesion development. This approach offers a potential therapeutic approach to the treatment of this disorder.","journal":"UNC Libraries","year":2021,"id":230605,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9502,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":601878,"name":"Laura A. Maile","orcid":null,"position":1,"is_corresponding":false},{"id":491591,"name":"Timothy C. Nichols","orcid":"0000-0001-8650-7096","position":2,"is_corresponding":false},{"id":609132,"name":"Walker H. Busby","orcid":null,"position":3,"is_corresponding":false},{"id":527845,"name":"Dwight A. Bellinger","orcid":null,"position":4,"is_corresponding":false},{"id":14173,"name":"Umadevi Veluvolu","orcid":null,"position":5,"is_corresponding":false},{"id":492844,"name":"Elizabeth P. Merricks","orcid":null,"position":6,"is_corresponding":false},{"id":837079,"name":"Michael A. Rowland","orcid":"0000-0002-6759-8225","position":7,"is_corresponding":false},{"id":365923,"name":"David R. Clemmons","orcid":"0000-0001-9946-788X","position":0,"is_corresponding":true}],"reference_count":0,"raw_metadata":null,"created_at":"2026-07-18T23:55:09.211909Z","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":[]}