{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T21:06:43Z","timestamp":1791234403288,"version":"4.1.0"},"reference-count":100,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"6","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2026,3,17]]},"abstract":"<jats:sec xml:lang=\"en\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p xml:lang=\"en\">Monocytes contribute to atherosclerosis by migrating into inflamed endothelium and differentiating into lipid\u2010laden macrophages. In people living with HIV, chronic inflammation increases atherosclerosis risk, yet the role of specific monocyte subsets remains unclear. We investigated how distinct monocyte populations contribute to vascular pathology in early HIV\u2010associated atherosclerosis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p xml:lang=\"en\">We profiled 123\u2009965 circulating monocytes using single\u2010cell RNA sequencing and integrated plasma microparticle proteomics in 32 individuals stratified by HIV and atherosclerosis status. Supervised learning identified cluster\u2010 and disease\u2010specific signatures, validated by platelet\u2010monocyte cocultures, reverse transcription\u2013quantitative polymerase chain reaction, bulk RNA sequencing, flow cytometry, and ELISA.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p xml:lang=\"en\">\n                      Seven monocyte clusters were identified, including a subset characterized by platelet\u2013monocyte complexes. Bulk RNA sequencing of platelet\u2013monocyte cocultures revealed platelet\u2010driven upregulation of genes involved in inflammation, lipid metabolism, oxidative stress, and endothelial adhesion. Platelet\u2013monocyte complex\u2013derived macrophages secreted higher levels of TGF\u2010\u03b2 (transforming growth factor\u2010\u03b2)\u00a0and IL\u201010 (interleukin\u201010), displayed decreased CD14 and increased CD80\/CD86 while retaining CD36, and promoted endothelial\u2010to\u2010mesenchymal transition (decreased expression of\n                      <jats:italic toggle=\"yes\">CDH5<\/jats:italic>\n                      and\n                      <jats:italic toggle=\"yes\">PECAM1<\/jats:italic>\n                      ; increased expression of\n                      <jats:italic toggle=\"yes\">S100A4<\/jats:italic>\n                      and markers of\u00a0vascular inflammation (\n                      <jats:italic toggle=\"yes\">ICAM1<\/jats:italic>\n                      ),\n                      <jats:italic toggle=\"yes\">VCAM<\/jats:italic>\n                      ), and IL\u20106 (interleukin\u20106), and CCL2\u00a0(C\u2010C motif chemokine ligand 2) secretion). Additionally, CD14\n                      <jats:sup>+<\/jats:sup>\n                      monocytes from HIV\n                      <jats:sup>+<\/jats:sup>\n                      atherosclerosis\u2010negative and HIV\n                      <jats:sup>+<\/jats:sup>\n                      atherosclerosis\u2010positive groups showed enhanced ROS\u2010NRF2 (reactive oxygen species\u2013nuclear factor erythroid 2\u2013related factor 2)\u00a0pathway activities, supported by increased basal and H\n                      <jats:sub>2<\/jats:sub>\n                      O\n                      <jats:sub>2<\/jats:sub>\n                      \u2010induced p90RSK phosphorylation, indicating oxidative stress priming.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p xml:lang=\"en\">\n                      Two monocyte clusters contribute independently to vascular immune dysregulation in people living with HIV. Platelet\u2013monocyte complex\u2013derived macrophages promote endothelial dysfunction while adopting a profibrotic cytokine profile. CD14\n                      <jats:sup>+<\/jats:sup>\n                      monocytes show heightened oxidative signaling and stress responses, consistent with vascular activation. Together, these mechanisms may accelerate atherosclerosis development in HIV, even in the absence of traditional cardiovascular risk factors.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/jaha.125.046482","type":"journal-article","created":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T11:34:07Z","timestamp":1773401647000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":3,"title":["Monocytes Defined by Platelet Interactions and Oxidative Stress Signaling Underlie HIV\u2010Associated Atherosclerosis"],"prefix":"10.1161","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2013-4850","authenticated-orcid":false,"given":"Ruoqiao H.","family":"Wang","sequence":"first","affiliation":[{"name":"University of Rochester School of Medicine and Dentistry","place":["Rochester"]},{"name":"University of Rochester School of Medicine and 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