{"doi":"10.1172/jci.insight.177229","title":"Caspase-4/11 promotes hyperlipidemia and chronic kidney disease–accelerated vascular inflammation by enhancing trained immunity","abstract":"To determine whether hyperlipidemia and chronic kidney disease (CKD) have a synergy in accelerating vascular inflammation via trained immunity (TI), we performed aortic pathological analysis and RNA-Seq of high-fat diet-fed (HFD-fed) 5/6 nephrectomy CKD (HFD+CKD) mice. We made the following findings: (a) HFD+CKD increased aortic cytosolic LPS levels, caspase-11 (CASP11) activation, and 998 gene expressions of TI pathways in the aorta (first-tier TI mechanism); (b) CASP11-/- decreased aortic neointima hyperplasia, aortic recruitment of macrophages, and casp11-gasdermin D-mediated cytokine secretion; (c) CASP11-/- decreased N-terminal gasdermin D (N-GSDMD) membrane expression on aortic endothelial cells and aortic IL-1B levels; (d) LPS transfection into human aortic endothelial cells resulted in CASP4 (human)/CASP11 (mouse) activation and increased N-GSDMD membrane expression; and (e) IL-1B served as the second-tier mechanism underlying HFD+CKD-promoted TI. Taken together, hyperlipidemia and CKD accelerated vascular inflammation by promoting 2-tier trained immunity.","journal":"JCI Insight","year":2024,"id":434220,"datarank":0.4434909602474495,"base_score":2.639057329615259,"endowment":2.639057329615259,"self_citation_contribution":0.3958585994422889,"citation_network_contribution":0.047632360805160597,"self_endowment_contribution":0.3958585994422889,"citer_contribution":0.047632360805160597,"corpus_percentile":null,"corpus_rank":null,"citation_count":13,"citer_count":6,"citers_with_citation_signal":3,"citers_with_endowment":3,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9514,"is_data_producer":true,"deposit_databanks":{"BioProject":["PRJNA1106364"]},"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":237313,"name":"Yifan Lu","orcid":"0000-0003-4461-0698","position":1,"is_corresponding":false},{"id":1240366,"name":"Lu Liu","orcid":"0000-0002-5890-3304","position":2,"is_corresponding":false},{"id":239127,"name":"Fatma Saaoud","orcid":null,"position":3,"is_corresponding":false},{"id":237315,"name":"Ying Shao","orcid":"0000-0001-5879-0154","position":4,"is_corresponding":false},{"id":237316,"name":"Keman Xu","orcid":"0000-0002-0816-1760","position":5,"is_corresponding":false},{"id":237314,"name":"Charles Drummer","orcid":"0000-0001-9059-1454","position":6,"is_corresponding":false},{"id":377728,"name":"Ramón Cueto","orcid":null,"position":7,"is_corresponding":false},{"id":643853,"name":"Huimin Shan","orcid":null,"position":8,"is_corresponding":false},{"id":267258,"name":"Xiaohua Jiang","orcid":"0000-0003-3325-6531","position":9,"is_corresponding":false},{"id":274033,"name":"Huaqing Zhao","orcid":"0000-0002-0953-4768","position":10,"is_corresponding":false},{"id":233134,"name":"Hong Wang","orcid":"0000-0001-6258-4070","position":11,"is_corresponding":false},{"id":233133,"name":"Xiaofeng Yang","orcid":"0000-0002-6854-6195","position":12,"is_corresponding":false},{"id":237312,"name":"Yu Sun","orcid":"0000-0002-0877-7186","position":0,"is_corresponding":true}],"reference_count":87,"raw_metadata":null,"created_at":"2026-07-19T01:59:53.957667Z","pmid":"39024553","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":[]}