{"doi":"10.1161/atvbaha.120.314189","title":"Atherosclerosis Impairs Naive CD4 T-Cell Responses via Disruption of Glycolysis","abstract":"Objective: CD4 T cells are important regulators of atherosclerotic progression. The metabolic profile of CD4 T cells controls their signaling and function, but how atherosclerosis affects T-cell metabolism is unknown. Here, we sought to determine the impact of atherosclerosis on CD4 T-cell metabolism and the contribution of such metabolic alterations to atheroprogression. Approach and Results: Using PCR arrays, we profiled the expression of metabolism genes in CD4 T cells from atherosclerotic apolipoprotein-E knockout mice fed a Western diet. These cells exhibited dysregulated expression of genes critically involved in glycolysis and fatty acid degradation, compared with those from animals fed a standard laboratory diet. We examined how T-cell metabolism was changed in either Western diet–fed apolipoprotein-E knockout mice or samples from patients with cardiovascular disease by measuring glucose uptake, activation, and proliferation in CD4 T cells. We found that naive CD4 T cells from Western diet–fed apolipoprotein-E knockout mice failed to uptake glucose and displayed impaired proliferation and activation, compared with CD4 T cells from standard laboratory diet–fed animals. Similarly, we observed that naive CD4 T-cell frequencies were reduced in the circulation of human subjects with high cardiovascular disease compared with low cardiovascular disease. Naive T cells from high cardiovascular disease subjects also showed reduced proliferative capacity. Conclusions: These results highlight the dysfunction that occurs in CD4 T-cell metabolism and immune responses during atherosclerosis. Targeting metabolic pathways within naive CD4 T cells could thus yield novel therapeutic approaches for improving CD4 T-cell responses against atheroprogression.","journal":"Arteriosclerosis Thrombosis and Vascular Biology","year":2021,"id":172702,"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":25,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9615,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":363869,"name":"Lindsey E. Padgett","orcid":"0000-0002-2925-0076","position":1,"is_corresponding":false},{"id":272882,"name":"Runpei Wu","orcid":null,"position":2,"is_corresponding":false},{"id":363871,"name":"Anh V. Nguyen","orcid":"0000-0001-6703-2291","position":3,"is_corresponding":false},{"id":709583,"name":"Chantel McSkimming","orcid":null,"position":4,"is_corresponding":false},{"id":271171,"name":"Huy Q. Dinh","orcid":"0000-0002-3307-1126","position":5,"is_corresponding":false},{"id":299945,"name":"Daniel J. Araujo","orcid":null,"position":6,"is_corresponding":false},{"id":363872,"name":"Angela M. Taylor","orcid":"0000-0003-4927-4320","position":7,"is_corresponding":false},{"id":363873,"name":"Coleen A. McNamara","orcid":"0000-0002-0049-9986","position":8,"is_corresponding":false},{"id":247023,"name":"Catherine C. Hedrick","orcid":"0000-0003-2045-4117","position":9,"is_corresponding":false},{"id":363870,"name":"Dalia E. Gaddis","orcid":"0000-0002-1527-1909","position":0,"is_corresponding":true}],"reference_count":46,"raw_metadata":null,"created_at":"2026-07-18T23:46:41.424716Z","pmid":"34320835","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":[]}