{"doi":"10.1093/cvr/cvac036","title":"Endothelial OCT4 is atheroprotective by preventing metabolic and phenotypic dysfunction","abstract":"AIMS: Until recently, the pluripotency factor Octamer (ATGCAAAT)-binding transcriptional factor 4 (OCT4) was believed to be dispensable in adult somatic cells. However, our recent studies provided clear evidence that OCT4 has a critical atheroprotective role in smooth muscle cells. Here, we asked if OCT4 might play a functional role in regulating endothelial cell (EC) phenotypic modulations in atherosclerosis. METHODS AND RESULTS: Specifically, we show that EC-specific Oct4 knockout resulted in increased lipid, LGALS3+ cell accumulation, and altered plaque characteristics consistent with decreased plaque stability. A combination of single-cell RNA sequencing and EC-lineage-tracing studies revealed increased EC activation, endothelial-to-mesenchymal transitions, plaque neovascularization, and mitochondrial dysfunction in the absence of OCT4. Furthermore, we show that the adenosine triphosphate (ATP) transporter, ATP-binding cassette (ABC) transporter G2 (ABCG2), is a direct target of OCT4 in EC and establish for the first time that the OCT4/ABCG2 axis maintains EC metabolic homeostasis by regulating intracellular heme accumulation and related reactive oxygen species production, which, in turn, contributes to atherogenesis. CONCLUSIONS: These results provide the first direct evidence that OCT4 has a protective metabolic function in EC and identifies vascular OCT4 and its signalling axis as a potential target for novel therapeutics.","journal":"Cardiovascular Research","year":2022,"id":246973,"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":35,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9649,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":677310,"name":"Svyatoslav Tkachenko","orcid":"0000-0001-8687-1576","position":1,"is_corresponding":false},{"id":693471,"name":"Malay Chaklader","orcid":"0000-0003-2192-7537","position":2,"is_corresponding":false},{"id":884286,"name":"Connor Pletz","orcid":null,"position":3,"is_corresponding":false},{"id":883831,"name":"Kanwardeep Singh","orcid":"0000-0003-3912-4847","position":4,"is_corresponding":false},{"id":452519,"name":"Gamze B. Bulut","orcid":"0000-0002-8344-3338","position":5,"is_corresponding":false},{"id":884287,"name":"Young min Han","orcid":null,"position":6,"is_corresponding":false},{"id":268418,"name":"Kelly Mitchell","orcid":"0000-0002-1124-7864","position":7,"is_corresponding":false},{"id":861662,"name":"Richard A. Baylis","orcid":"0000-0001-7040-7920","position":8,"is_corresponding":false},{"id":883832,"name":"Andrey A. Kuzmin","orcid":"0000-0002-8629-2045","position":9,"is_corresponding":false},{"id":455368,"name":"Bo Hu","orcid":"0000-0003-0606-7639","position":10,"is_corresponding":false},{"id":240691,"name":"Justin D. Lathia","orcid":"0000-0003-3168-7290","position":11,"is_corresponding":false},{"id":571766,"name":"Olga Stenina‐Adognravi","orcid":null,"position":12,"is_corresponding":false},{"id":278591,"name":"Eugene A. Podrez","orcid":"0000-0002-9550-6965","position":13,"is_corresponding":false},{"id":278593,"name":"Tatiana V. Byzova","orcid":"0000-0002-2615-875X","position":14,"is_corresponding":false},{"id":353055,"name":"Gary K. Owens","orcid":"0000-0002-7119-9657","position":15,"is_corresponding":false},{"id":883833,"name":"Olga A. Cherepanova","orcid":"0000-0003-0045-8102","position":16,"is_corresponding":false},{"id":883830,"name":"Junchul Shin","orcid":"0000-0002-4959-6680","position":0,"is_corresponding":true}],"reference_count":78,"raw_metadata":null,"created_at":"2026-07-19T00:23:48.622830Z","pmid":"35325071","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":[]}