{"doi":"10.1186/s12933-024-02473-y","title":"Endothelial KLF11 is a novel protector against diabetic atherosclerosis","abstract":"BACKGROUND: Atherosclerotic cardiovascular diseases remain the leading cause of mortality in diabetic patients, with endothelial cell (EC) dysfunction serving as the initiating step of atherosclerosis, which is exacerbated in diabetes. Krüppel-like factor 11 (KLF11), known for its missense mutations leading to the development of diabetes in humans, has also been identified as a novel protector of vascular homeostasis. However, its role in diabetic atherosclerosis remains unexplored. METHODS: background by feeding a diabetogenic diet with cholesterol (DDC). Single-cell RNA sequencing (scRNA-seq) was utilized to profile EC dysfunction in diabetic atherosclerosis. Additionally, gain- and loss-of-function experiments were conducted to investigate the role of KLF11 in hyperglycemia-induced endothelial cell dysfunction. RESULTS: We found that endothelial KLF11 deficiency significantly accelerates atherogenesis under diabetic conditions, whereas KLF11 overexpression remarkably inhibits it. scRNA-seq profiling demonstrates that loss of KLF11 increases endothelial-to-mesenchymal transition (EndMT) during atherogenesis under diabetic conditions. Utilizing gain- and loss-of-function approaches, our in vitro study reveals that KLF11 significantly inhibits EC inflammatory activation and TXNIP-induced EC oxidative stress, as well as Notch1/Snail-mediated EndMT under high glucose exposure. CONCLUSION: Our study demonstrates that endothelial KLF11 is an endogenous protective factor against diabetic atherosclerosis. These findings indicate that manipulating KLF11 could be a promising approach for developing novel therapies for diabetes-related cardiovascular complications.","journal":"Cardiovascular Diabetology","year":2024,"id":435846,"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":12,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9621,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":659593,"name":"Yang Zhao","orcid":"0000-0002-1362-9823","position":1,"is_corresponding":false},{"id":471094,"name":"Wenying Liang","orcid":"0000-0001-9985-6674","position":2,"is_corresponding":false},{"id":243091,"name":"Haocheng Lu","orcid":"0000-0002-5740-8010","position":3,"is_corresponding":false},{"id":341502,"name":"Hongyu Liu","orcid":"0000-0002-8111-3941","position":4,"is_corresponding":false},{"id":1122839,"name":"Yongjie Deng","orcid":null,"position":5,"is_corresponding":false},{"id":243093,"name":"Tianqing Zhu","orcid":"0000-0003-3592-5276","position":6,"is_corresponding":false},{"id":243095,"name":"Yanhong Guo","orcid":"0000-0002-3334-9159","position":7,"is_corresponding":false},{"id":1243444,"name":"Lin Chang","orcid":"0000-0003-1878-6155","position":8,"is_corresponding":false},{"id":243096,"name":"Minerva T. Garcia-Barrio","orcid":"0000-0002-3381-3847","position":9,"is_corresponding":false},{"id":945271,"name":"Y. Eugene Chen","orcid":"0009-0000-8983-739X","position":10,"is_corresponding":false},{"id":243097,"name":"Jifeng Zhang","orcid":"0000-0001-5161-4705","position":11,"is_corresponding":false},{"id":243090,"name":"Guizhen Zhao","orcid":"0000-0002-2648-8986","position":0,"is_corresponding":true}],"reference_count":69,"raw_metadata":null,"created_at":"2026-07-19T02:00:08.103086Z","pmid":"39462409","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":[]}