{"doi":"10.3389/fcvm.2021.777098","title":"Hematopoietic Cell-Specific SLC37A2 Deficiency Accelerates Atherosclerosis in LDL Receptor-Deficient Mice","abstract":"Macrophages play a central role in the pathogenesis of atherosclerosis. Our previous study demonstrated that solute carrier family 37 member 2 (SLC37A2), an endoplasmic reticulum-anchored phosphate-linked glucose-6-phosphate transporter, negatively regulates macrophage Toll-like receptor activation by fine-tuning glycolytic reprogramming in vitro . Whether macrophage SLC37A2 impacts in vivo macrophage inflammation and atherosclerosis under hyperlipidemic conditions is unknown. We generated hematopoietic cell-specific SLC37A2 knockout and control mice in C57Bl/6 Ldlr −/− background by bone marrow transplantation. Hematopoietic cell-specific SLC37A2 deletion in Ldlr −/− mice increased plasma lipid concentrations after 12-16 wks of Western diet induction, attenuated macrophage anti-inflammatory responses, and resulted in more atherosclerosis compared to Ldlr −/− mice transplanted with wild type bone marrow. Aortic root intimal area was inversely correlated with plasma IL-10 levels, but not total cholesterol concentrations, suggesting inflammation but not plasma cholesterol was responsible for increased atherosclerosis in bone marrow SLC37A2-deficient mice. Our in vitro study demonstrated that SLC37A2 deficiency impaired IL-4-induced macrophage activation, independently of glycolysis or mitochondrial respiration. Importantly, SLC37A2 deficiency impaired apoptotic cell-induced glycolysis, subsequently attenuating IL-10 production. Our study suggests that SLC37A2 expression is required to support alternative macrophage activation in vitro and in vivo . In vivo disruption of hematopoietic SLC37A2 accelerates atherosclerosis under hyperlipidemic pro-atherogenic conditions.","journal":"Frontiers in Cardiovascular Medicine","year":2021,"id":203109,"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":6,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9553,"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":237684,"name":"Zhan Wang","orcid":"0000-0002-4225-8136","position":1,"is_corresponding":false},{"id":249630,"name":"Allison K. Meyers","orcid":"0000-0002-7399-1779","position":2,"is_corresponding":false},{"id":65888,"name":"Jennifer H. Madenspacher","orcid":null,"position":3,"is_corresponding":false},{"id":446721,"name":"Manal Zabalawi","orcid":null,"position":4,"is_corresponding":false},{"id":783793,"name":"Qianyi Zhang","orcid":"0000-0003-0973-0037","position":5,"is_corresponding":false},{"id":446722,"name":"Elena Boudyguina","orcid":null,"position":6,"is_corresponding":false},{"id":291317,"name":"Fang‐Chi Hsu","orcid":"0000-0002-3310-184X","position":7,"is_corresponding":false},{"id":458825,"name":"Charles E. McCall","orcid":"0000-0001-6176-8177","position":8,"is_corresponding":false},{"id":285814,"name":"Cristina M. Furdui","orcid":"0000-0003-3771-7999","position":9,"is_corresponding":false},{"id":299668,"name":"John S. Parks","orcid":"0000-0002-5227-8915","position":10,"is_corresponding":false},{"id":270412,"name":"Michael B. Fessler","orcid":"0000-0002-8262-8613","position":11,"is_corresponding":false},{"id":237683,"name":"Xuewei Zhu","orcid":"0000-0002-8606-0930","position":12,"is_corresponding":false},{"id":446723,"name":"Qingxia Zhao","orcid":null,"position":0,"is_corresponding":true}],"reference_count":65,"raw_metadata":null,"created_at":"2026-07-18T23:51:14.206397Z","pmid":"34957260","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":[]}