{"doi":"10.3390/ijms242115526","title":"Proteomic Determinants of Variation in Cholesterol Efflux: Observations from the Dallas Heart Study","abstract":"High-density lipoproteins (HDLs) are promising targets for predicting and treating atherosclerotic cardiovascular disease (ASCVD), as they mediate removal of excess cholesterol from lipid-laden macrophages that accumulate in the vasculature. This functional property of HDLs, termed cholesterol efflux capacity (CEC), is inversely associated with ASCVD. HDLs are compositionally diverse, associating with >250 different proteins, but their relative contribution to CEC remains poorly understood. Our goal was to identify and define key HDL-associated proteins that modulate CEC in humans. The proteomic signature of plasma HDL was quantified in 36 individuals in the multi-ethnic population-based Dallas Heart Study (DHS) cohort that exhibited persistent extremely high (>=90th%) or extremely low CEC (<=10th%) over 15 years. Levels of apolipoprotein (Apo)A-I associated ApoC-II, ApoC-III, and ApoA-IV were differentially correlated with CEC in high (r = 0.49, 0.41, and −0.21 respectively) and low (r = −0.46, −0.41, and 0.66 respectively) CEC groups (p for heterogeneity (pHet) = 0.03, 0.04, and 0.003 respectively). Further, we observed that levels of ApoA-I with ApoC-III, complement C3 (CO3), ApoE, and plasminogen (PLMG) were inversely associated with CEC in individuals within the low CEC group (r = −0.11 to −0.25 for subspecies with these proteins vs. r = 0.58 to 0.65 for subspecies lacking these proteins; p < 0.05 for heterogeneity). These findings suggest that enrichment of specific proteins on HDLs and, thus, different subspecies of HDLs, differentially modulate the removal of cholesterol from the vasculature.","journal":"International Journal of Molecular Sciences","year":2023,"id":351867,"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":9,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9492,"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":722711,"name":"Sneha Deodhar","orcid":null,"position":1,"is_corresponding":false},{"id":722710,"name":"Suzanne Saldanha","orcid":null,"position":2,"is_corresponding":false},{"id":108539,"name":"Olle Melander","orcid":"0000-0002-2581-484X","position":3,"is_corresponding":false},{"id":504420,"name":"Fahim Abbasi","orcid":"0000-0002-3932-8375","position":4,"is_corresponding":false},{"id":486730,"name":"Ryan W. Pearce","orcid":"0000-0001-5341-6059","position":5,"is_corresponding":false},{"id":1096918,"name":"Timothy S. Collier","orcid":"0000-0002-1102-8741","position":6,"is_corresponding":false},{"id":996992,"name":"Michael J. McPhaul","orcid":"0000-0003-4399-5733","position":7,"is_corresponding":false},{"id":311094,"name":"Jeremy D. Furtado","orcid":"0000-0002-5258-1869","position":8,"is_corresponding":false},{"id":39750,"name":"Frank M. Sacks","orcid":"0000-0003-1341-1995","position":9,"is_corresponding":false},{"id":1096919,"name":"Nathaniel J. Merrill","orcid":"0000-0002-1998-0980","position":10,"is_corresponding":false},{"id":28979,"name":"Jason McDermott","orcid":"0000-0003-2961-2572","position":11,"is_corresponding":false},{"id":698262,"name":"John Melchior","orcid":"0000-0003-3781-2566","position":12,"is_corresponding":false},{"id":293943,"name":"Anand Rohatgi","orcid":"0000-0003-0164-2382","position":13,"is_corresponding":false},{"id":1097416,"name":"Anamika Gangwar","orcid":null,"position":0,"is_corresponding":true}],"reference_count":64,"raw_metadata":null,"created_at":"2026-07-19T01:12:45.897709Z","pmid":"37958510","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":[]}