{"doi":"10.1161/atvbaha.108.169680","title":"Absence of Hyperlipidemia in LDL Receptor-Deficient Mice Having Apolipoprotein B100 Without the Putative Receptor-Binding Sequences","abstract":"<jats:p>\n            <jats:bold>\n              <jats:italic>Objective—</jats:italic>\n            </jats:bold>\n            To examine the effects of apoB100 structure, specifically a mutation in the LDLr binding region, on the production of LDL and development of atherosclerosis in vivo.\n          </jats:p>\n          <jats:p>\n            <jats:bold>\n              <jats:italic>Methods and Results—</jats:italic>\n            </jats:bold>\n            <jats:italic>Ldlr</jats:italic>\n            <jats:sup>−/−</jats:sup>\n            <jats:italic>Apobec1</jats:italic>\n            <jats:sup>−/−</jats:sup>\n            mice lacking the LDLR and apoB editing enzyme accumulated LDL in plasma and developed severe atherosclerosis when they had wild-type apoB100. In marked contrast, in\n            <jats:italic>Ldlr</jats:italic>\n            <jats:sup>−/−</jats:sup>\n            <jats:italic>Apobec1</jats:italic>\n            <jats:sup>−/−</jats:sup>\n            mice carrying the Apob100-β mutation, in the 2 putative LDLR-binding domains of apoB prevented both LDL accumulation and atherosclerosis. Intestinal absorption of lipids and triglyceride secretion from the liver were not affected. However, the VLDL particles with apoB100-β were larger in volume by about 70%, and carried approximately four times as much apoE per particle. ApoB100-β synthesis rate in the primary hepatocytes was normal, but its intracellular degradation was enhanced. Additionally, mutant apoB100 VLDL cleared from the circulation more quickly in vivo through apoE-LRP-mediated mechanism than VLDL with wild-type apoB100. In contrast, uptake of the 2 VLDL by macrophages were not different.\n          </jats:p>\n          <jats:p>\n            <jats:bold>\n              <jats:italic>Conclusion—</jats:italic>\n            </jats:bold>\n            While conformational change to apoB100 during conversion of VLDL to LDL exposes LDLR binding domains and facilitates LDLR-mediated lipoprotein clearance, it may also inhibit LRP-mediated VLDL uptake and contribute to LDL accumulation in familial hypercholesterolemia.\n          </jats:p>","journal":"Arteriosclerosis, Thrombosis, and Vascular Biology","year":2008,"id":616738,"datarank":0.38474240361923057,"base_score":2.5649493574615367,"endowment":2.5649493574615367,"self_citation_contribution":0.38474240361923057,"citation_network_contribution":0.0,"self_endowment_contribution":0.38474240361923057,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":12,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":592589,"name":"Michael K. Altenburg","orcid":null,"position":1,"is_corresponding":false},{"id":411725,"name":"Rosemary L. Walzem","orcid":"0000-0002-9913-7810","position":2,"is_corresponding":false},{"id":1590206,"name":"Lori T. Scanga","orcid":null,"position":3,"is_corresponding":false},{"id":446134,"name":"Nobuyo Maeda","orcid":"0000-0002-2248-3299","position":4,"is_corresponding":false},{"id":278179,"name":"Lance A. Johnson","orcid":"0000-0003-0134-7586","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Absence of Hyperlipidemia in LDL Receptor-Deficient Mice Having Apolipoprotein B100 Without the Putative Receptor-Binding Sequences","abstract":"<jats:p>\n            <jats:bold>\n              <jats:italic>Objective—</jats:italic>\n            </jats:bold>\n            To examine the effects of apoB100 structure, specifically a mutation in the LDLr binding region, on the production of LDL and development of atherosclerosis in vivo.\n          </jats:p>\n          <jats:p>\n            <jats:bold>\n              <jats:italic>Methods and Results—</jats:italic>\n            </jats:bold>\n            <jats:italic>Ldlr</jats:italic>\n            <jats:sup>−/−</jats:sup>\n            <jats:italic>Apobec1</jats:italic>\n            <jats:sup>−/−</jats:sup>\n            mice lacking the LDLR and apoB editing enzyme accumulated LDL in plasma and developed severe atherosclerosis when they had wild-type apoB100. In marked contrast, in\n            <jats:italic>Ldlr</jats:italic>\n            <jats:sup>−/−</jats:sup>\n            <jats:italic>Apobec1</jats:italic>\n            <jats:sup>−/−</jats:sup>\n            mice carrying the Apob100-β mutation, in the 2 putative LDLR-binding domains of apoB prevented both LDL accumulation and atherosclerosis. Intestinal absorption of lipids and triglyceride secretion from the liver were not affected. However, the VLDL particles with apoB100-β were larger in volume by about 70%, and carried approximately four times as much apoE per particle. ApoB100-β synthesis rate in the primary hepatocytes was normal, but its intracellular degradation was enhanced. Additionally, mutant apoB100 VLDL cleared from the circulation more quickly in vivo through apoE-LRP-mediated mechanism than VLDL with wild-type apoB100. In contrast, uptake of the 2 VLDL by macrophages were not different.\n          </jats:p>\n          <jats:p>\n            <jats:bold>\n              <jats:italic>Conclusion—</jats:italic>\n            </jats:bold>\n            While conformational change to apoB100 during conversion of VLDL to LDL exposes LDLR binding domains and facilitates LDLR-mediated lipoprotein clearance, it may also inhibit LRP-mediated VLDL uptake and contribute to LDL accumulation in familial hypercholesterolemia.\n          </jats:p>","is_dataset_classified":null,"base_score":2.5649493574615367,"endowment":2.5649493574615367,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"18617647","pmcid":null,"openalex_id":"https://openalex.org/W2054097176","authors":[],"funders":[],"total_grants":0,"fwci":1.1959,"citation_percentile":0.79806947,"influential_citations":0,"citation_trend":[{"year":2012,"count":2},{"year":2017,"count":1},{"year":2023,"count":1},{"year":2025,"count":1}],"oa_status":"bronze","license":null,"oa_locations":[{"url":"https://www.ahajournals.org/doi/pdf/10.1161/ATVBAHA.108.169680","host_type":"journal"},{"url":"https://www.ahajournals.org/doi/pdf/10.1161/ATVBAHA.108.169680","host_type":"publisher"},{"url":"https://www.ahajournals.org/doi/full/10.1161/ATVBAHA.108.169680","host_type":"publisher"},{"url":"https://doi.org/10.1161/atvbaha.108.169680","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/18617647","host_type":"repository"},{"url":"http://citeseerx.ist.psu.edu/viewdoc/summary?doi=10.1.1.496.9249","host_type":""},{"url":"http://citeseerx.ist.psu.edu/viewdoc/summary?doi=10.1.1.998.2881","host_type":""},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/5268125","host_type":"repository"}],"fields_of_study":["Diabetes, Cardiovascular Risks, and Lipoproteins","Lipoproteins and Cardiovascular Health","Atherosclerosis and Cardiovascular Diseases"],"mesh_terms":["APOBEC-1 Deaminase","Animals","Binding Sites","Cytidine Deaminase","Dietary Fats","Disease Models, Animal","Hyperlipidemias","Lipoproteins, LDL","Lipoproteins, VLDL","Mice, Inbred C57BL","Mutation","Particle Size","Protein Binding","Protein Conformation","Receptors, LDL","Time Factors","Macrophages, Peritoneal","Mice, Knockout","Hepatocytes","Atherosclerosis","Mice","Apolipoprotein B-100"],"keywords":["Hyperlipidemia","Apolipoprotein B","LDL receptor","Receptor","Internal medicine","Endocrinology","Apolipoprotein E","Chemistry","Medicine","Biology","Cholesterol","Lipoprotein","Diabetes mellitus"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-02T23:43:20.219874Z","pmid":null,"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":[]}