{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T08:21:56Z","timestamp":1793089316522,"version":"4.5.0"},"reference-count":42,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"17","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2021,9,7]]},"abstract":"<jats:sec xml:lang=\"en\">\n            <jats:title>Background<\/jats:title>\n            <jats:p xml:lang=\"en\">ApoAI (apolipoproteins AI) and apoAII (apolipoprotein AII) are structural and functional proteins of high\u2010density lipoproteins (HDL) which undergo post\u2010translational modifications at specific residues, creating distinct proteoforms. While specific post\u2010translational modifications have been reported to alter apolipoprotein function, the full spectrum of apoAI and apoAII proteoforms and their associations with cardiometabolic phenotype remains unknown. Herein, we comprehensively characterize apoAI and apoAII proteoforms detectable in serum and their post\u2010translational modifications and quantify their associations with cardiometabolic health indices.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Methods and Results<\/jats:title>\n            <jats:p xml:lang=\"en\">Using top\u2010down proteomics (mass\u2010spectrometric analysis of intact proteins), we analyzed paired serum samples from 150 CARDIA (Coronary Artery Risk Development in Young Adults) study participants from year 20 and 25 exams. Measuring 15 apoAI and 9 apoAII proteoforms, 6 of which carried novel post\u2010translational modifications, we quantified associations between percent proteoform abundance and key cardiometabolic indices. Canonical (unmodified) apoAI had inverse associations with HDL cholesterol and HDL\u2010cholesterol efflux, and positive associations with obesity indices (body mass index, waist circumference), and triglycerides, whereas glycated apoAI showed positive associations with serum glucose and diabetes mellitus. Fatty\u2010acid\u2012modified ApoAI proteoforms had positive associations with HDL cholesterol and efflux, and inverse associations with obesity indices and triglycerides. Truncated and dimerized proteoforms of apoAII were associated with HDL cholesterol (positively) and obesity indices (inversely). Several proteoforms had no significant associations with phenotype.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p xml:lang=\"en\">Associations between apoAI and AII and cardiometabolic indices are proteoform\u2010specific. These results provide \u201cproof\u2010of\u2010concept\u201d that precise chemical characterization of human apolipoproteins will yield improved insights into the complex pathways through which proteins signify and mediate health and disease.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/jaha.120.019890","type":"journal-article","created":{"date-parts":[[2021,9,2]],"date-time":"2021-09-02T09:08:20Z","timestamp":1630573700000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":31,"title":["Spectrum of Apolipoprotein AI and Apolipoprotein AII Proteoforms and Their Associations With Indices of Cardiometabolic Health: The CARDIA Study"],"prefix":"10.1161","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8781-1329","authenticated-orcid":false,"given":"John T.","family":"Wilkins","sequence":"first","affiliation":[{"name":"Department of Medicine (Cardiology) and Department of Preventive Medicine Northwestern University Chicago IL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henrique S.","family":"Seckler","sequence":"additional","affiliation":[{"name":"Department of Chemistry Chemistry of Life Processes Institute and Proteomics Center of Excellence Northwestern University Evanston IL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6130-2948","authenticated-orcid":false,"given":"Jonathan","family":"Rink","sequence":"additional","affiliation":[{"name":"Department of Medicine (Urology) Northwestern University Chicago IL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip D.","family":"Compton","sequence":"additional","affiliation":[{"name":"Department of Chemistry Chemistry of Life Processes Institute and Proteomics Center of Excellence Northwestern University Evanston IL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6334-1046","authenticated-orcid":false,"given":"Luca","family":"Fornelli","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology University of Oklahoma Norman OK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C. Shad","family":"Thaxton","sequence":"additional","affiliation":[{"name":"Department of Medicine (Urology) Northwestern University Chicago IL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6951-2923","authenticated-orcid":false,"given":"Rich","family":"LeDuc","sequence":"additional","affiliation":[{"name":"Department of Chemistry Chemistry of Life Processes Institute and Proteomics Center of Excellence Northwestern University Evanston IL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7232-0543","authenticated-orcid":false,"given":"David","family":"Jacobs","sequence":"additional","affiliation":[{"name":"Division of Epidemiology and Community Health School of Public Health University of Minnesota Minneapolis MN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter F.","family":"Doubleday","sequence":"additional","affiliation":[{"name":"Department of Chemistry Chemistry of Life Processes Institute and Proteomics Center of Excellence Northwestern University Evanston IL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3540-3956","authenticated-orcid":false,"given":"Allan","family":"Sniderman","sequence":"additional","affiliation":[{"name":"Mike and Valeria Rosenbloom Centre for Cardiovascular Prevention Department of Medicine McGill University Health Centre Montreal Quebec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0847-6110","authenticated-orcid":false,"given":"Donald M.","family":"Lloyd\u2010Jones","sequence":"additional","affiliation":[{"name":"Department of Medicine (Cardiology) and Department of Preventive Medicine Northwestern University Chicago IL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neil L.","family":"Kelleher","sequence":"additional","affiliation":[{"name":"Department of Chemistry Chemistry of Life Processes 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