{"doi":"10.1016/j.jbc.2023.105425","title":"Enhanced Akt3 kinase activity reduces atherosclerosis in hyperlipidemic mice in a gender-dependent manner","abstract":"Akt3 is one of the three members of the serine/threonine protein kinase B (AKT) family, which regulates multiple cellular processes. We have previously demonstrated that global knockout of Akt3 in mice promotes atherogenesis in a macrophage-dependent manner. Whether enhanced Akt3 kinase activity affects atherogenesis is not known. In this study, we crossed atherosclerosis-prone ApoE −/− mice with a mouse strain that has enhanced Akt3 kinase activity (Akt3 nmf350 ) and assessed atherosclerotic lesion formation and the role of macrophages in atherogenesis. Significant reduction in atherosclerotic lesion area and macrophage accumulation in lesions were observed in ApoE −/− /Akt3 nmf350 mice fed a Western-type diet. Experiments using chimeric ApoE −/− mice with either ApoE −/− /Akt3 nmf350 bone marrow or ApoE −/− bone marrow cells showed that enhanced Akt3 activity specifically in bone marrow-derived cells is atheroprotective. The atheroprotective effect of Akt3 nmf350 was more pronounced in male mice. In line with this result, the release of the pro-inflammatory cytokines IL-6, MCP1, TNF-α, and MIP-1α was reduced by macrophages from male but not female ApoE −/− /Akt3 nmf350 mice. Levels of IL-6 and TNF-α were also reduced in atherosclerotic lesions of ApoE −/− /Akt3 nmf350 male mice compared to ApoE −/− mice. Macrophages from male ApoE −/− /Akt3 nmf350 mice were also more resistant to apoptosis in vitro and in vivo and tended to have more pronounced M2 polarization in vitro . These findings demonstrated that enhanced Akt3 kinase activity in macrophages protects mice from atherosclerosis in hyperlipidemic mice in a gender-dependent manner.","journal":"Journal of Biological Chemistry","year":2023,"id":379209,"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":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9589,"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":753987,"name":"Jessica Altemus","orcid":null,"position":1,"is_corresponding":false},{"id":351845,"name":"Liang Ding","orcid":"0000-0002-1043-0923","position":2,"is_corresponding":false},{"id":1143656,"name":"О. Е. Черепанова","orcid":"0000-0001-7775-6488","position":3,"is_corresponding":false},{"id":278593,"name":"Tatiana V. Byzova","orcid":"0000-0002-2615-875X","position":4,"is_corresponding":false},{"id":278591,"name":"Eugene A. Podrez","orcid":"0000-0002-9550-6965","position":5,"is_corresponding":false},{"id":1143655,"name":"Lifang Zhang","orcid":"0000-0003-2463-9813","position":0,"is_corresponding":true}],"reference_count":48,"raw_metadata":null,"created_at":"2026-07-19T01:16:52.622552Z","pmid":"37926285","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":[]}