{"doi":"10.1016/j.jmccpl.2023.100046","title":"Genetic deletion of 12/15 lipoxygenase delays vascular remodeling and limits cardiorenal dysfunction after pressure overload","abstract":"The lipid metabolizing enzyme 12/15 lipoxygenase (12/15LOX) induces proinflammatory responses that may increase cardiovascular and renal complications after cardiac insult. To define the role of 12/15LOX, 8–12-week-old male C57BL/6J wild-type (WT; n = 49) and 12/15LOX−/− mice (n = 50) were subject to transverse aortic constriction (TAC) and monitored for 7, 28, and 56 days (d) post-TAC. Compared with WT, 12/15LOX−/− mice experienced less left ventricle (LV) dysfunction with limited LV hypertrophy and lung edema post-TAC. 12/15LOX deletion decreased TAC-induced proinflammatory mediators 12-HETE and prostaglandins with modulation in mir-7a-5p, mir 26a-5p, miR-21e-5p, and miR-107-3p during chronic remodeling period (after d28). At d7 post-TAC, 12/15LOX−/− mice showed increased cardiac gene expression of Arg-1 and the prostanoid receptors EP2 and EP4. The EP4 receptor expression was consistently elevated from d7 till d56 in 12/15LOX−/− mice post-TAC compared with WT controls. Post-TAC, wheat germ agglutinin staining revealed less cardiomyocyte hypertrophy at d28 and d56 in 12/15LOX−/− mice compared with WT. TAC-induced vascular remodeling was marked by disruption in the endothelium, evident by irregular CD31 staining and increased alpha-smooth muscle actin (α-SMA) in WT mice at d28 and d56. Compared to WT, 12/15LOX−/− mice exhibited a diminished expression of NGAL in the kidney, suggesting that 12/15LOX−/− reduced cardiorenal dysfunction post-TAC. In WT-TAC mice, structural analyses of the kidney revealed glomerular swelling during the maladaptive phase of heart failure, with decreases in the capsula glomeruli space and glomerular sclerosis compared to 12/15LOX−/− mice. Overall, vascular and kidney inflammation markers were higher in WT than in 12/15LOX−/− post-TAC. Thus, deletion of 12/15LOX limits LV hypertrophy associated with perivascular inflammation and cardiorenal remodeling after pressure overload. Deficiency of 12/15 LOX serves a dual role in delaying an early adaptive interstitial remodeling with long-term protective effects on cardiac hypertrophy and cardiac fibrosis and detrimental adverse vascular remodeling during later maladaptive remodeling after pressure overload.","journal":"Journal of Molecular and Cellular Cardiology Plus","year":2023,"id":379794,"datarank":0.1625488289626013,"base_score":0.6931471805599453,"endowment":0.6931471805599453,"self_citation_contribution":0.10397207708399181,"citation_network_contribution":0.058576751878609494,"self_endowment_contribution":0.10397207708399181,"citer_contribution":0.058576751878609494,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":1,"citers_with_citation_signal":1,"citers_with_endowment":1,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9596,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":395362,"name":"Vasundhara Kain","orcid":"0000-0001-8571-8553","position":1,"is_corresponding":false},{"id":238232,"name":"Da‐Zhi Wang","orcid":"0000-0003-1774-6549","position":2,"is_corresponding":false},{"id":927261,"name":"Donald G. Rokosh","orcid":null,"position":3,"is_corresponding":false},{"id":371996,"name":"Sumanth D. Prabhu","orcid":"0000-0002-7247-7241","position":4,"is_corresponding":false},{"id":345499,"name":"Ganesh V. Halade","orcid":"0000-0002-5351-9354","position":5,"is_corresponding":false},{"id":1144459,"name":"Dae Hyun Lee","orcid":"0000-0001-8141-0404","position":0,"is_corresponding":true}],"reference_count":44,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T01:16:56.650289Z","pmid":"39802176","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":[]}