{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T05:57:48Z","timestamp":1782280668652,"version":"3.54.5"},"posted":{"date-parts":[[2025,5,4]]},"group-title":"Biochemistry","reference-count":66,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,5,4]],"date-time":"2025-05-04T00:00:00Z","timestamp":1746316800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,5,4]]},"abstract":"<jats:sec>\n                  <jats:title>BACKGROUND<\/jats:title>\n                  <jats:p>Over 10 million patients undergoing non-cardiac surgery annually experience major cardiovascular complications within 30 days, many due to destabilized atherosclerotic plaques. Reverse cholesterol transport (RCT), a key pathway for cholesterol removal by HDL and apoA-I, is critical in preventing plaque progression. While surgery-induced inflammation is known to impair HDL function, its effects on RCT and plaque stability remain unclear.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>METHODS<\/jats:title>\n                  <jats:p>\n                    To isolate the impact of surgical inflammation, independent of blood loss, we developed an abdominal laparotomy model in\n                    <jats:italic>apoE<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>-\/-<\/jats:italic>\n                    <\/jats:sup>\n                    mice on a Western diet, minimizing blood loss and avoiding perioperative blood sampling. We assessed plasma cholesterol efflux capacity, performed proteomic analysis of HDL, and analyzed atherosclerotic plaques for lipid content, perilipin-2 (PLIN2), cleaved-caspase-3 (c-Casp-3), and necrotic core expansion. A novel dual-label, dual-cell-type\n                    <jats:italic>in vivo<\/jats:italic>\n                    RCT model was developed to compare RCT from macrophage-derived (BMDMs) and vascular smooth muscle cells (VSMCs)-derived foam cells. Recombinant apoA-I (rApoA-I) was tested for therapeutic rescue of impaired RCT.\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>RESULTS<\/jats:title>\n                  <jats:p>\n                    Surgery significantly reduced RCT for at least 48 hours, paralleled by a drop in cholesterol efflux capacity and inflammatory remodeling of HDL, marked by elevated serum amyloid A (SAA1\/2) and reduced apoA-I. Plaques showed a 1.6-fold increase in intracellular lipids and PLIN2 expression at 24 hours post-surgery, with elevated c-Casp-3 indicating lipid-driven apoptosis. Foam cell analysis revealed increased PLIN2 in both CD45\n                    <jats:sup>+<\/jats:sup>\n                    (leukocyte) and CD45\n                    <jats:sup>-<\/jats:sup>\n                    (non-leukocyte) subtypes, with leukocyte foam cells expressing higher PLIN2. c-Casp-3\n                    <jats:sup>+<\/jats:sup>\n                    apoptotic cells were predominantly PLIN2\n                    <jats:sup>high<\/jats:sup>\n                    and of both leukocytic and non-leukocytic origin. By day 15, the necrotic core area increased by 1.5-fold with sustained loss of plaque cellularity. Using our dual-cell-type RCT model, we found that surgery significantly impaired BMDM RCT\n                    <jats:italic>in vivo<\/jats:italic>\n                    , while VSMC RCT remained largely unaffected, highlighting foam cell subtype-specific vulnerability to surgical inflammation. These findings were mirrored in general surgery patients, whose postoperative plasma exhibited markedly reduced cholesterol efflux capacity. In mice, rApoA-I treatment partially restored RCT and reduced plaque lipid accumulation.\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>CONCLUSIONS<\/jats:title>\n                  <jats:p>Surgical inflammation acutely impairs HDL function and RCT, triggering lipid accumulation, foam cell apoptosis, and accelerated plaque destabilization independent of blood loss. Immediate restoration of apoA-I at the time of surgery, aiming to counteract the acute phase response, may offer a targeted strategy to reduce postoperative cardiovascular risk.<\/jats:p>\n                <\/jats:sec>","DOI":"10.1101\/2025.05.02.651357","type":"posted-content","created":{"date-parts":[[2025,5,4]],"date-time":"2025-05-04T21:05:12Z","timestamp":1746392712000},"source":"Crossref","is-referenced-by-count":1,"title":["Postoperative Stress Accelerates Atherosclerosis through Inflammatory Remodeling of the HDL Proteome and Impaired Reverse Cholesterol Transport"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2223-0117","authenticated-orcid":false,"given":"Dominique M.","family":"Boucher","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valerie","family":"Rochon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9359-2783","authenticated-orcid":false,"given":"Thomas","family":"Laval","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victoria","family":"Lorant","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abigail","family":"Carter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christina","family":"Emerton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathan","family":"Joyce","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nysa","family":"Vinayak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marlena","family":"Scaffidi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca C.","family":"Auer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9532-032X","authenticated-orcid":false,"given":"Scott M.","family":"Gordon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6831-5047","authenticated-orcid":false,"given":"Mireille I.","family":"Ouimet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2025050613100491000_2025.05.02.651357v1.1","doi-asserted-by":"publisher","DOI":"10.1097\/ALN.0000000000000113"},{"key":"2025050613100491000_2025.05.02.651357v1.2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1502824"},{"key":"2025050613100491000_2025.05.02.651357v1.3","doi-asserted-by":"publisher","DOI":"10.1097\/00000542-199001000-00025"},{"key":"2025050613100491000_2025.05.02.651357v1.4","doi-asserted-by":"publisher","DOI":"10.1186\/s12872-025-04534-w"},{"key":"2025050613100491000_2025.05.02.651357v1.5","doi-asserted-by":"publisher","DOI":"10.1038\/nri3520"},{"key":"2025050613100491000_2025.05.02.651357v1.6","unstructured":"Patel, S. 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