{"doi":"10.1016/j.jlr.2023.100456","title":"Serum opacity factor normalizes erythrocyte morphology in Scarb1−/− mice in an HDL-free cholesterol-dependent way","abstract":"Compared to wild-type (WT) mice, high-density lipoprotein (HDL)-receptor-deficient (Scarb1-/-) mice have higher plasma levels of free cholesterol (FC)-rich HDL and exhibit multiple pathologies associated with a high mol% FC in ovaries, platelets, and erythrocytes which are reversed by lowering HDL. Bacterial serum opacity factor (SOF) catalyzes the opacification of plasma by targeting and quantitatively converting HDL to neo HDL (HDL remnant), a cholesterol ester-rich microemulsion, and lipid-free APOA1. SOF delivery with an adeno-associated virus (AAVSOF) constitutively lowers plasma HDL-FC and reverses female infertility in Scarb1-/- mice in an HDL-dependent way. We tested whether AAVSOF delivery to Scarb1-/- mice will normalize erythrocyte morphology in an HDL-FC dependent way. We determined erythrocyte morphology and FC content (mol%) in three groups—WT, untreated Scarb1-/- (control), and Scarb1-/- mice receiving AAVSOF—and correlated these with their respective HDL-mol% FC. Plasma-, HDL- and tissue-lipid compositions were also determined. Plasma- and HDL-mol% FC positively correlated across all groups. Among Scarb1-/- mice, AAVSOF treatment normalized reticulocyte number, erythrocyte morphology and erythrocyte-mol% FC. Erythrocyte-mol% FC positively correlated with HDL-mol% FC and with both the number of reticulocytes and abnormal erythrocytes. AAVSOF treatment also reduced FC of extravascular tissues to a lesser extent. HDL-FC spontaneously transfers from plasma HDL to cell membranes. AAVSOF treatment lowers erythrocyte-FC and normalizes erythrocyte morphology and lipid composition by reducing HDL-mol% FC.","journal":"Journal of Lipid Research","year":2023,"id":388936,"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":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9546,"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":531111,"name":"Dedipya Yelamanchili","orcid":null,"position":1,"is_corresponding":false},{"id":530359,"name":"Jing Liu","orcid":"0000-0002-1019-0843","position":2,"is_corresponding":false},{"id":78541,"name":"Antonio M. Gotto","orcid":"0000-0001-8076-6783","position":3,"is_corresponding":false},{"id":426606,"name":"Corina Rosales","orcid":"0000-0002-9068-2775","position":4,"is_corresponding":false},{"id":426607,"name":"Baiba K. Gillard","orcid":"0000-0002-2527-5102","position":5,"is_corresponding":false},{"id":367542,"name":"Henry J. Pownall","orcid":"0000-0001-8412-506X","position":6,"is_corresponding":false},{"id":634677,"name":"Ziyi Wang","orcid":"0000-0003-1884-8053","position":0,"is_corresponding":true}],"reference_count":69,"raw_metadata":null,"created_at":"2026-07-19T01:18:22.323414Z","pmid":"37821077","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":[]}