{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T17:58:36Z","timestamp":1790791116948,"version":"4.1.0"},"reference-count":67,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T00:00:00Z","timestamp":1790467200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T00:00:00Z","timestamp":1790467200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100007129","name":"Natural Science Foundation of Shandong Province","doi-asserted-by":"publisher","award":["ZR2025QB42"],"award-info":[{"award-number":["ZR2025QB42"]}],"id":[{"id":"10.13039\/501100007129","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002858","name":"China Postdoctoral Science Foundation","doi-asserted-by":"publisher","award":["2025T181071"],"award-info":[{"award-number":["2025T181071"]}],"id":[{"id":"10.13039\/501100002858","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002858","name":"China Postdoctoral Science Foundation","doi-asserted-by":"publisher","award":["2024M751904"],"award-info":[{"award-number":["2024M751904"]}],"id":[{"id":"10.13039\/501100002858","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["advanced.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Advanced Science"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Atherosclerosis is a chronic inflammatory disease driven by senescent vascular smooth muscle cells (VSMCs). Salvianolic acid A (SAA) exhibits cardiovascular protective effects; however, its role in atherosclerosis remains unclear. This study aimed to investigate the effects and targets of SAA in atherosclerosis. In vitro studies were performed in senescent VSMCs with heat shock protein 90 alpha (HSP90\u03b1)\u00a0overexpression or knockdown, with or without SAA treatment. In vivo, ApoE\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice fed a high\u2010fat diet were treated with SAA and adeno\u2010associated virus\u2010mediated VSMC\u2010specific HSP90\u03b1 overexpression or knockdown. SAA promoted apoptosis in senescent VSMCs by inhibiting HSP90\u03b1. This inhibition promoted ubiquitin\u2010proteasome\u2010dependent degradation of protein kinase B (AKT) and activation of PRKR\u2010Like Endoplasmic Reticulum Kinase (PERK) signaling. SAA increased endoplasmic reticulum\u2010mitochondrial contacts and mitochondrial calcium uptake. These effects were reversed by HSP90\u03b1 overexpression. In ApoE\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice, SAA reduced the burden of senescent VSMCs, decreased the size of plaque, and increased the stability of the fibrous cap. VSMC\u2010specific HSP90\u03b1 knockdown mimicked the protective effects of SAA, whereas HSP90\u03b1 overexpression reversed SAA\u2010mediated effects on disease. SAA reduces the burden of senescent VSMCs in atherosclerosis by inhibiting the scaffold function of HSP90\u03b1 which maintains the AKT\u2010PERK interaction, to reactivate PERK signaling, thereby alleviating disease progression.\n                  <\/jats:p>","DOI":"10.1002\/advs.77891","type":"journal-article","created":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T18:00:31Z","timestamp":1790532031000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Salvianolic Acid a Disrupts the HSP90\u03b1\u2010AKT\u2010PERK Ternary Complex to Alleviate Atherosclerosis by Activating Endoplasmic Reticulum Stress of Senescent Vascular Smooth Muscle Cells"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-2104-4252","authenticated-orcid":false,"given":"Xiuya","family":"Guan","sequence":"first","affiliation":[{"name":"College of Traditional Chinese Medicine Shandong University of Traditional Chinese 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China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3132-3809","authenticated-orcid":false,"given":"Lei","family":"Zhang","sequence":"additional","affiliation":[{"name":"First Clinical Medical College Shandong University of Traditional Chinese Medicine  Jinan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Lin","sequence":"additional","affiliation":[{"name":"Innovation Research Institute of Traditional Chinese Medicine Shandong University of Traditional Chinese Medicine  Jinan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan","family":"Li","sequence":"additional","affiliation":[{"name":"Innovation Research Institute of Traditional Chinese Medicine Shandong University of Traditional Chinese Medicine  Jinan 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