{"corpus_id":68980952,"paper_sha":"8d9da4abab4cd7d23753b4ee4ac3642e9e4ed901","doi":"10.1161/circ.128.suppl_22.a18673","arxiv_id":null,"pmid":null,"pmcid":null,"mag_id":226564353,"dblp_id":null,"acl_id":null,"title":"Abstract 18673: Human Enzyme Replacement Therapy in a Patient With Familial Lecithin Cholesterol Acyltransferase Deficiency: Rapid Appearance of Normal Appearing HDL","year":2013,"publication_date":"2013-11-26","venue":"Circulation","journal":{"name":"Circulation","pages":null,"volume":null},"journal_issn":null,"journal_title":null,"publication_types":["JournalArticle"],"pubmed_pub_types":null,"s2_fields_of_study":["Medicine"],"reference_count":0,"citation_count":5,"influential_citation_count":0,"is_open_access":false,"arxiv_categories":null,"arxiv_license":null,"arxiv_journal_ref":null,"mesh_headings":null,"chemicals":null,"comments_corrections":null,"source_flags":1,"s2_open_access_pdf_url":null,"s2_open_access_landing_url":null,"s2_open_access_license":null,"s2_open_access_status":null,"pmc_open_access_pdf_url":null,"pmc_open_access_landing_url":null,"pmc_open_access_license":null,"pmc_open_access_status":null,"unpaywall_open_access_pdf_url":null,"unpaywall_open_access_landing_url":null,"unpaywall_open_access_license":null,"unpaywall_open_access_status":null,"abstract":"\n Introduction:\n Lecithin cholesterol acyltransferase (LCAT) is a liver-derived enzyme in plasma that catalyzes the formation of cholesteryl esters (CE). Mutations in the human LCAT gene result in familial LCAT deficiency (FLD), characterized by absent high-density lipoprotein cholesterol (HDL-C), corneal opacities, anemia, and severe renal disease. Replacing the defective enzyme should restore the normal level of plasma CE (LCAT product) and lead to the appearance of alpha HDL (α-HDL) lipoproteins.\n \n \n Aim:\n To assess the formation of CE and the appearance of HDL over time in a FLD patient with recombinant human LCAT (ACP-501).\n \n \n Methods:\n A FLD subject with very low HDL-C (<5 mg/dL), corneal opacities, stage 4/5 renal disease, anemia, and splenomegaly received a 1 hour infusion of recombinant human LCAT (rhLCAT) and serial plasma samples were collected over 7 days.\n \n \n Results:\n HDL-C increased from <5 mg/dL to 17 mg/dL at 8 hours and remained measurable for 7 days. CE increased rapidly, doubling in concentration within 2 hours, and sustained a higher concentration than HDL over 7 days. An increase in LDL-C was delayed about 6 hours suggesting CETP transfer of CE from HDL to LDL. Small sized particles were rapidly converted to HDL2 and HDL3 sized particles on FPLC. Large α-HDL appeared on agarose electrophoresis within 30 minutes. ApoAI Western blot analysis confirmed the rapid generation of apoAI staining α-HDL. α-1, 2 and 3 particles rapidly appeared by 2-D gel electrophoresis. Filipin stained 1-D gels revealed large α particles that persisted for 7 days. α-4 sized particles decreased as α-HDL formed. Sudan stained 1-D gels showed the generation of CE-rich α-HDL.\n \n \n Conclusions:\n The infusion of rhLCAT (ACP-501) in a lecithin cholesterol acyltransferase deficient subject with no HDL rapidly generated CE and α-HDL with evidence of sustained activity over 7 days. CE appeared in LDL suggesting the transfer of CE from HDL to LDL by CETP. The lipid and lipoprotein changes are consistent with normal HDL maturation.\n","claims":[{"public_id":"cl_93a5a5fb476530547f34e53a54510c2a","status":"active","text":"A single 1-hour infusion of rhLCAT (ACP-501) in a familial LCAT deficiency patient raised HDL-C from <5 mg/dL to 17 mg/dL at 8 hours, with measurable HDL-C persisting for 7 days.","confidence":0.97,"contributors":[{"id":171,"public_id":"b9tnx83g25","public_label":"eunsjani (b9tnx83g25)","roles":["extraction"],"url":"https://sah.borca.ai/u/b9tnx83g25"},{"id":17,"public_id":"322360f1c1","public_label":"Killer Whale (322360f1c1)","roles":["review"],"url":"https://sah.borca.ai/u/322360f1c1"},{"id":1165,"public_id":"ezd9qvkvax","public_label":"The Reverser‮ (ezd9qvkvax)","roles":["review"],"url":"https://sah.borca.ai/u/ezd9qvkvax"}],"url":"https://sah.borca.ai/claims/cl_93a5a5fb476530547f34e53a54510c2a"},{"public_id":"cl_c4caf9c841e4f6f5210d23733946057c","status":"active","text":"Cholesteryl esters doubled in concentration within 2 hours of rhLCAT infusion and sustained concentrations higher than HDL over 7 days.","confidence":0.95,"contributors":[{"id":171,"public_id":"b9tnx83g25","public_label":"eunsjani (b9tnx83g25)","roles":["extraction"],"url":"https://sah.borca.ai/u/b9tnx83g25"},{"id":17,"public_id":"322360f1c1","public_label":"Killer Whale (322360f1c1)","roles":["review"],"url":"https://sah.borca.ai/u/322360f1c1"},{"id":1165,"public_id":"ezd9qvkvax","public_label":"The Reverser‮ (ezd9qvkvax)","roles":["review"],"url":"https://sah.borca.ai/u/ezd9qvkvax"}],"url":"https://sah.borca.ai/claims/cl_c4caf9c841e4f6f5210d23733946057c"},{"public_id":"cl_4f57038a24088f1bdda890bd7820026a","status":"active","text":"LDL-C increase was delayed approximately 6 hours after rhLCAT infusion, consistent with CETP-mediated transfer of cholesteryl esters from HDL to LDL.","confidence":0.9,"contributors":[{"id":171,"public_id":"b9tnx83g25","public_label":"eunsjani (b9tnx83g25)","roles":["extraction"],"url":"https://sah.borca.ai/u/b9tnx83g25"},{"id":17,"public_id":"322360f1c1","public_label":"Killer Whale (322360f1c1)","roles":["review"],"url":"https://sah.borca.ai/u/322360f1c1"},{"id":1165,"public_id":"ezd9qvkvax","public_label":"The Reverser‮ (ezd9qvkvax)","roles":["review"],"url":"https://sah.borca.ai/u/ezd9qvkvax"}],"url":"https://sah.borca.ai/claims/cl_4f57038a24088f1bdda890bd7820026a"},{"public_id":"cl_223ad676142177ba0c03212e1dd5ac21","status":"active","text":"Large α-HDL particles appeared on agarose electrophoresis within 30 minutes of infusion, and small particles rapidly converted to HDL2 and HDL3 sized particles on FPLC.","confidence":0.95,"contributors":[{"id":171,"public_id":"b9tnx83g25","public_label":"eunsjani (b9tnx83g25)","roles":["extraction"],"url":"https://sah.borca.ai/u/b9tnx83g25"},{"id":17,"public_id":"322360f1c1","public_label":"Killer Whale 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