{"corpus_id":205721657,"paper_sha":"b7ceaf6e9557684e8afd48dca50d0f90257f0e73","doi":"10.1016/j.atherosclerosis.2014.09.034","arxiv_id":null,"pmid":25463101,"pmcid":null,"mag_id":2086448825,"dblp_id":null,"acl_id":null,"title":"Altered lipidome and antioxidative activity of small, dense HDL in normolipidemic rheumatoid arthritis: relevance of inflammation.","year":2014,"publication_date":"2014-12-01","venue":"Atherosclerosis","journal":{"name":"Atherosclerosis","pages":"\n          652-60\n        ","volume":"237 2"},"journal_issn":null,"journal_title":null,"publication_types":["JournalArticle"],"pubmed_pub_types":["Journal Article","Research Support, Non-U.S. Gov't"],"s2_fields_of_study":["Medicine","Chemistry"],"reference_count":53,"citation_count":51,"influential_citation_count":3,"is_open_access":true,"arxiv_categories":null,"arxiv_license":null,"arxiv_journal_ref":null,"mesh_headings":[{"d":"Aged","mj":false,"ui":"D000368"},{"d":"Antioxidants","mj":false,"qs":[{"q":"chemistry","mj":true,"ui":"Q000737"}],"ui":"D000975"},{"d":"Arthritis, Rheumatoid","mj":false,"qs":[{"q":"blood","mj":true,"ui":"Q000097"}],"ui":"D001172"},{"d":"Aryldialkylphosphatase","mj":false,"qs":[{"q":"blood","mj":false,"ui":"Q000097"}],"ui":"D043303"},{"d":"Cardiovascular Diseases","mj":false,"qs":[{"q":"metabolism","mj":false,"ui":"Q000378"}],"ui":"D002318"},{"d":"Female","mj":false,"ui":"D005260"},{"d":"Humans","mj":false,"ui":"D006801"},{"d":"Inflammation","mj":false,"ui":"D007249"},{"d":"Lipids","mj":false,"qs":[{"q":"blood","mj":true,"ui":"Q000097"},{"q":"chemistry","mj":false,"ui":"Q000737"}],"ui":"D008055"},{"d":"Lipoproteins","mj":false,"qs":[{"q":"blood","mj":false,"ui":"Q000097"}],"ui":"D008074"},{"d":"Lipoproteins, HDL","mj":false,"qs":[{"q":"chemistry","mj":true,"ui":"Q000737"}],"ui":"D008075"},{"d":"Middle Aged","mj":false,"ui":"D008875"},{"d":"Oxidative Stress","mj":false,"ui":"D018384"},{"d":"Phospholipases A2","mj":false,"qs":[{"q":"blood","mj":false,"ui":"Q000097"}],"ui":"D054467"},{"d":"Postmenopause","mj":false,"ui":"D017698"}],"chemicals":[{"n":"Antioxidants","ui":"D000975","reg":"0"},{"n":"Lipids","ui":"D008055","reg":"0"},{"n":"Lipoproteins","ui":"D008074","reg":"0"},{"n":"Lipoproteins, HDL","ui":"D008075","reg":"0"},{"n":"Phospholipases A2","ui":"D054467","reg":"EC 3.1.1.4"},{"n":"Aryldialkylphosphatase","ui":"D043303","reg":"EC 3.1.8.1"},{"n":"PON1 protein, human","ui":"C468406","reg":"EC 3.1.8.1"}],"comments_corrections":null,"source_flags":5,"s2_open_access_pdf_url":"https://ri.conicet.gov.ar/bitstream/11336/30536/2/CONICET_Digital_Nro.aa98a64d-9197-4315-a219-300dc3ca3075_A.pdf","s2_open_access_landing_url":"https://www.semanticscholar.org/paper/b7ceaf6e9557684e8afd48dca50d0f90257f0e73","s2_open_access_license":"CCBYNCSA","s2_open_access_status":"GREEN","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":"OBJECTIVE\nHigh-density lipoprotein (HDL) particles exert potent antiatherogenic activities, including antioxidative actions, which are relevant to attenuation of atherosclerosis progression. Such activities are enriched in small, dense HDL and can be compromised under conditions of chronic inflammation like rheumatoid arthritis (RA). However, structure-function relationships of HDL largely remain indeterminate.\n\n\nMETHODS\nThe relationships between HDL structure and function were evaluated in normolipidemic patients with active RA (DAS28 > 3.2; n = 12) and in normolipidemic age-matched controls (n = 10). Small, dense HDL3b and 3c particles were isolated from plasma or serum by density gradient ultracentrifugation and their physicochemical characteristics, lipidome (by LC/MS/MS) and antioxidative function (as protection of normolipidemic LDL from free radical-induced oxidation) were evaluated.\n\n\nRESULTS\nAs expected, active RA patients featured significantly elevated plasma levels of high-sensitivity C-reactive protein (hsCRP; p < 0.001) and serum amyloid A (SAA; p < 0.01) relative to controls. Antioxidative activity and weight % chemical composition of small, dense HDL did not differ between RA patients and controls (p > 0.05), whereas HDL phosphosphingolipidome was significantly altered in RA. Subgroup analyses revealed that RA patients featuring high levels of inflammation (hsCRP>10 mg/l) possessed small, dense HDL with reduced antioxidative activities (p < 0.01). Furthermore, antioxidative activity of HDL was inversely correlated with plasma hsCRP (p < 0.01).\n\n\nCONCLUSIONS\nThese data revealed that (i) despite normolipidemic state, the lipidome of small, dense HDL was altered in RA and (ii) high levels of inflammation can be responsible for the functional deficiency of small, dense HDL in RA.","claims":[{"public_id":"cl_8edda115fa54cc864f8d8303c78045c8","status":"active","text":"Despite normolipidemia, the lipidome of small, dense HDL was altered in rheumatoid arthritis.","confidence":0.97,"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/claims/cl_8edda115fa54cc864f8d8303c78045c8"},{"public_id":"cl_dfe0054e47f153940d45605b5903b322","status":"active","text":"HDL antioxidative activity was inversely correlated with plasma high-sensitivity C-reactive protein.","confidence":0.93,"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/claims/cl_dfe0054e47f153940d45605b5903b322"},{"public_id":"cl_d67802d74529e78ff1e44019dab72bfa","status":"active","text":"High inflammation levels were associated with reduced antioxidative activity of small, dense HDL in rheumatoid arthritis.","confidence":0.95,"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/claims/cl_d67802d74529e78ff1e44019dab72bfa"},{"public_id":"cl_73c98b1ef7238baffce3f3effbe13215","status":"active","text":"Overall antioxidative activity and weight percent chemical composition of small, dense HDL did not differ between rheumatoid arthritis patients and controls.","confidence":0.9,"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/claims/cl_73c98b1ef7238baffce3f3effbe13215"}],"concepts":[{"public_id":"co_0052fac48b8fdfb710567bfa10e53e7d","status":"active","name":"lipidome","description":"The full set of lipid species measured in the small, dense HDL particles by mass spectrometry.","types":["molecular profile"],"aliases":[],"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/concepts/co_0052fac48b8fdfb710567bfa10e53e7d"},{"public_id":"co_0ff5982aa4d6912fab3d4c7c08874c47","status":"active","name":"rheumatoid arthritis","description":"A chronic inflammatory disease studied here in normolipidemic patients with active disease.","types":["disease"],"aliases":["RA"],"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/concepts/co_0ff5982aa4d6912fab3d4c7c08874c47"},{"public_id":"co_11b2bb62aa175c57877169d4fcae7f3a","status":"active","name":"controls","description":"Age-matched normolipidemic comparison participants without rheumatoid arthritis.","types":["comparison group"],"aliases":[],"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/concepts/co_11b2bb62aa175c57877169d4fcae7f3a"},{"public_id":"co_55a6b9ea06b934c544b7c10a5d67dc9c","status":"active","name":"plasma","description":"The blood fraction from which HDL particles were isolated and hsCRP was measured.","types":["biospecimen"],"aliases":[],"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/concepts/co_55a6b9ea06b934c544b7c10a5d67dc9c"},{"public_id":"co_5c681a8d4c2bc549810ef912c333eb16","status":"active","name":"antioxidative activity","description":"The ability of HDL to protect normolipidemic LDL from free radical-induced oxidation.","types":["functional property"],"aliases":["antioxidative function"],"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/concepts/co_5c681a8d4c2bc549810ef912c333eb16"},{"public_id":"co_a4c054fc7b7eb2e781beb44841d16530","status":"active","name":"serum amyloid A","description":"An acute-phase inflammatory protein measured in plasma or serum.","types":["biomarker"],"aliases":["SAA"],"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/concepts/co_a4c054fc7b7eb2e781beb44841d16530"},{"public_id":"co_a5702fad968f77bdf37bf86bdda2ee7d","status":"active","name":"weight percent chemical composition","description":"The relative chemical composition of HDL expressed as mass percent of its components.","types":["composition measure"],"aliases":["weight % chemical composition"],"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/concepts/co_a5702fad968f77bdf37bf86bdda2ee7d"},{"public_id":"co_eac37b16d5de0440aa000cc7c0f4c4b9","status":"active","name":"high-sensitivity C-reactive protein","description":"A blood inflammatory biomarker used here to quantify systemic 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