{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T16:29:10Z","timestamp":1792427350590,"version":"4.5.0"},"reference-count":38,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"19","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2018,10,2]]},"abstract":"\n Background<\/jats:title>\n \n HIV<\/jats:styled-content>\n + people are at increased risk of coronary artery disease, but the responsible mechanisms are incompletely understood. Proprotein convertase subtilisin\/kexin type 9 (\n PCSK<\/jats:styled-content>\n 9) is traditionally recognized for its importance in cholesterol metabolism; however, recent data suggest an additional, low\u2010density lipoprotein receptor\u2013independent adverse effect on endothelial cell inflammation and function. We tested the hypotheses that\n PCSK<\/jats:styled-content>\n 9 levels are increased and that abnormal coronary endothelial function is related to\n PCSK<\/jats:styled-content>\n 9 serum levels in\n HIV<\/jats:styled-content>\n + individuals.\n <\/jats:p>\n <\/jats:sec>\n \n Methods and Results<\/jats:title>\n \n Forty\u2010eight\n HIV<\/jats:styled-content>\n + participants receiving antiretroviral therapy with suppressed viral replication, without coronary artery disease, and 15 age\u2010 and low\u2010density lipoprotein cholesterol\u2013matched healthy\n HIV\u2212<\/jats:styled-content>\n subjects underwent magnetic resonance imaging to measure coronary endothelial function, quantified as percentage change in coronary artery cross\u2010sectional area during isometric handgrip exercise, an endothelial\u2010dependent stressor; and blood was obtained for serum\n PCSK<\/jats:styled-content>\n 9 and systemic vascular biomarkers. Data are presented as mean\u00b1SD. Mean serum\n PCSK<\/jats:styled-content>\n 9 was 65% higher in the\n HIV<\/jats:styled-content>\n + subjects (302\u00b1146\u00a0ng\/\n mL<\/jats:styled-content>\n ) than in the\n HIV<\/jats:styled-content>\n \u2212 controls (183\u00b152\u00a0ng\/\n mL<\/jats:styled-content>\n ,\n P<\/jats:italic>\n <0.0001). Coronary endothelial function was significantly reduced in the\n HIV<\/jats:styled-content>\n + versus\n HIV<\/jats:styled-content>\n \u2212 subjects (percentage change in coronary artery cross\u2010sectional area, 2.9\u00b19.6% versus 11.1\u00b13.7%;\n P<\/jats:italic>\n <0.0001) and inversely related to\n PCSK<\/jats:styled-content>\n 9 (\n R<\/jats:italic>\n =\u22120.51,\n P<\/jats:italic>\n <0.0001). Markers of endothelial activation and injury, P\u2010selectin and thrombomodulin, were also significantly increased in the\n HIV<\/jats:styled-content>\n + subjects; and P\u2010selectin was directly correlated with serum\n PCSK<\/jats:styled-content>\n 9 (\n R<\/jats:italic>\n =0.31,\n P<\/jats:italic>\n =0.0144).\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n Serum\n PCSK<\/jats:styled-content>\n 9 levels are increased in treated\n HIV<\/jats:styled-content>\n + individuals and are associated with abnormal coronary endothelial function, an established measure of vascular health.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1161\/jaha.118.009996","type":"journal-article","created":{"date-parts":[[2018,9,25]],"date-time":"2018-09-25T09:01:03Z","timestamp":1537866063000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":55,"title":["Coronary Endothelial Dysfunction Is Associated With Elevated Serum PCSK9 Levels in People With HIV Independent of Low\u2010Density Lipoprotein Cholesterol"],"prefix":"10.1161","volume":"7","author":[{"given":"Thorsten M.","family":"Leucker","sequence":"first","affiliation":[{"name":"Division of Cardiology Department of Medicine Johns Hopkins University School of Medicine Baltimore MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert G.","family":"Weiss","sequence":"additional","affiliation":[{"name":"Division of Cardiology Department of Medicine Johns Hopkins University School of Medicine Baltimore MD"},{"name":"Division of Magnetic Resonance Research Department of Radiology Johns Hopkins University School of Medicine Baltimore MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Sch\u00e4r","sequence":"additional","affiliation":[{"name":"Division of Magnetic Resonance Research Department of Radiology Johns Hopkins University School of Medicine Baltimore MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriele","family":"Bonanno","sequence":"additional","affiliation":[{"name":"Division of Cardiology Department of Medicine Johns Hopkins University School of Medicine Baltimore MD"},{"name":"Division of Magnetic Resonance Research Department of Radiology Johns Hopkins University School of Medicine Baltimore MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lena","family":"Mathews","sequence":"additional","affiliation":[{"name":"Division of Cardiology Department of Medicine Johns Hopkins University School of Medicine Baltimore MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven R.","family":"Jones","sequence":"additional","affiliation":[{"name":"Division of Cardiology Department of Medicine Johns Hopkins University School of Medicine Baltimore MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Todd T.","family":"Brown","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Diabetes and Metabolism Department of Medicine Johns Hopkins University School of Medicine Baltimore MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Moore","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases Department of Medicine Johns Hopkins University School of Medicine Baltimore MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yohannes","family":"Afework","sequence":"additional","affiliation":[{"name":"Division of Magnetic Resonance Research Department of Radiology Johns Hopkins University School of Medicine Baltimore MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gary","family":"Gerstenblith","sequence":"additional","affiliation":[{"name":"Division of Cardiology Department of Medicine Johns Hopkins University School of Medicine Baltimore MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Allison G.","family":"Hays","sequence":"additional","affiliation":[{"name":"Division of Cardiology Department of Medicine Johns Hopkins University School of Medicine Baltimore 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