{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T01:04:43Z","timestamp":1792458283419,"version":"4.5.0"},"reference-count":51,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"8","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["ATVB"],"published-print":{"date-parts":[[2023,8]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>\n                      Apo CIII (apolipoprotein CIII) is an important regulator of triglyceride metabolism and was associated with cardiovascular risk in several cohorts. It is present in 4 major proteoforms, a native peptide (CIII\n                      <jats:sub>0a<\/jats:sub>\n                      ), and glycosylated proteoforms with zero (CIII\n                      <jats:sub>0b<\/jats:sub>\n                      ), 1 (CIII\n                      <jats:sub>1<\/jats:sub>\n                      , most abundant), or 2 (CIII\n                      <jats:sub>2<\/jats:sub>\n                      ) sialic acids, which may differentially modify lipoprotein metabolism. We studied the relationships of these proteoforms with plasma lipids and cardiovascular risk.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>Apo CIII proteoforms were measured by mass spectrometry immunoassay in baseline plasma samples of 5791 participants of Multi-Ethnic Study of Atherosclerosis, an observational community-based cohort. Standard plasma lipids were collected for up to 16 years and cardiovascular events (myocardial infarction, resuscitated cardiac arrest, or stroke) were adjudicated for up to 17 years.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      Apo CIII proteoform composition differed by age, sex, race and ethnicity, body mass index, and fasting glucose. Notably, CIII\n                      <jats:sub>1<\/jats:sub>\n                      was lower in older participants, men and Black and Chinese (versus White) participants, and higher in obesity and diabetes. In contrast, CIII\n                      <jats:sub>2<\/jats:sub>\n                      was higher in older participants, men, Black, and Chinese persons, and lower in Hispanic individuals and obesity. Higher CIII\n                      <jats:sub>2<\/jats:sub>\n                      to CIII\n                      <jats:sub>1<\/jats:sub>\n                      ratio (CIII\n                      <jats:sub>2<\/jats:sub>\n                      \/III\n                      <jats:sub>1<\/jats:sub>\n                      ) was associated with lower triglycerides and higher HDL (high-density lipoprotein) in cross-sectional and longitudinal models, independently of clinical and demographic risk factors and total apo CIII. The associations of CIII\n                      <jats:sub>0a<\/jats:sub>\n                      \/III\n                      <jats:sub>1<\/jats:sub>\n                      and CIII\n                      <jats:sub>0b<\/jats:sub>\n                      \/III\n                      <jats:sub>1<\/jats:sub>\n                      with plasma lipids were weaker and varied through cross-sectional and longitudinal analyses. Total apo CIII and CIII\n                      <jats:sub>2<\/jats:sub>\n                      \/III\n                      <jats:sub>1<\/jats:sub>\n                      were positively associated with cardiovascular disease risk (n=669 events, hazard ratios, 1.14 [95% CI, 1.04\u20131.25] and 1.21 [1.11\u20131.31], respectively); however, the associations were attenuated after adjustment for clinical and demographic characteristics (1.07 [0.98\u20131.16]; 1.07 [0.97\u20131.17]). In contrast, CIII\n                      <jats:sub>0b<\/jats:sub>\n                      \/III\n                      <jats:sub>1<\/jats:sub>\n                      was inversely associated with cardiovascular disease risk even after full adjustment including plasma lipids (0.86 [0.79\u20130.93]).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>Our data indicate differences in clinical and demographic relationships of apo CIII proteoforms, and highlight the importance of apo CIII proteoform composition in predicting future lipid patterns and cardiovascular disease risk.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/atvbaha.123.319035","type":"journal-article","created":{"date-parts":[[2023,6,15]],"date-time":"2023-06-15T05:00:21Z","timestamp":1686805221000},"page":"1560-1571","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":17,"title":["Apo CIII Proteoforms, Plasma Lipids, and Cardiovascular Risk in MESA"],"prefix":"10.1161","volume":"43","author":[{"given":"Shripad","family":"Sinari","sequence":"first","affiliation":[{"name":"Mel and Enid Zuckerman College of Public Health, University of Arizona, Tucson (S.S., D.B.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6671-6250","authenticated-orcid":true,"given":"Juraj","family":"Koska","sequence":"additional","affiliation":[{"name":"Phoenix VA Health Care System, AZ (J.K.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yueming","family":"Hu","sequence":"additional","affiliation":[{"name":"Isoformix, Inc, Phoenix, AZ (Y.H., D.N.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeremy","family":"Furtado","sequence":"additional","affiliation":[{"name":"Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA (J.F., M.K.J.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4729-7545","authenticated-orcid":true,"given":"Majken K.","family":"Jensen","sequence":"additional","affiliation":[{"name":"Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA (J.F., M.K.J.)."},{"name":"Department of Public Health, University of Copenhagen, Denmark (M.K.J.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9616-1946","authenticated-orcid":true,"given":"Matthew J.","family":"Budoff","sequence":"additional","affiliation":[{"name":"Lundquist Institute at Harbor-University of California, Los Angeles (UCLA), Torrance (M.J.B.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dobrin","family":"Nedelkov","sequence":"additional","affiliation":[{"name":"Isoformix, Inc, Phoenix, AZ (Y.H., D.N.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robyn L.","family":"McClelland","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, University of Washington, Seattle (R.L.M.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dean","family":"Billheimer","sequence":"additional","affiliation":[{"name":"Mel and Enid Zuckerman College of Public Health, University of Arizona, Tucson (S.S., D.B.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Reaven","sequence":"additional","affiliation":[{"name":"College of Health Solutions, Arizona State University, Phoenix (P.R.)."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.E015701"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.117.309493"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/s0006-291x(72)80149-9"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-2275(20)34342-X"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI111711"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1194\/M900346-JLR200"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.106.622514"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.108.784785"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.cir.102.16.1886"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.metabol.2004.05.004"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.cir.90.1.42"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.metabol.2017.03.016"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.117.031276"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.117.007824"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacl.2020.10.006"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI127308"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1308027"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1161524"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/s0021-9150(01)00409-9"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2016.11.065"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1400283"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-2275(20)32459-7"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-2275(20)38224-9"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1172\/jci110532"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.272.50.31348"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.P064816"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.2337\/db09-0206"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.M500455-JLR200"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-2275(20)37352-1"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0144138"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1093\/aje\/kwf113"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1001\/archinte.168.12.1333"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.109.197830"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-94-009-4109-0"},{"key":"e_1_3_3_36_2","volume-title":"Statistical Analysis of Proteomics, Metabolomics, and Lipidomics Data Using Mass Spectrometry","author":"Sinari S","year":"2016","unstructured":"Sinari, S, Nedelkov, D, Reaven, P, Billheimer, D. 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