{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T03:45:03Z","timestamp":1792122303192,"version":"4.4.0"},"reference-count":62,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2025,6,11]],"date-time":"2025-06-11T00:00:00Z","timestamp":1749600000000},"content-version":"vor","delay-in-days":10,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,6,1]],"date-time":"2025-06-01T00:00:00Z","timestamp":1748736000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Biochem &amp;amp; Molecular Tox"],"published-print":{"date-parts":[[2025,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Atherosclerosis is a complex disease involving a series of interrelated events, among which endothelial cell dysfunction and vascular smooth muscle cell proliferation play pivotal roles in the early formation of atherosclerotic plaques. Sphingosine 1\u2010phosphate, a product of sphingomyelin metabolism, serves as a signaling molecule implicated in the pathogenesis of atherosclerosis and other conditions by binding to sphingosine 1\u2010phosphate receptors (S1PRs). However, the precise mechanism by which S1PRs influence atherosclerosis remains incompletely understood. Here, we identified a dual role for S1PR2 in vascular cells treated with oxidized\u2010low\u2010density lipoprotein. In smooth muscle cells, decreased S1PR2 upregulated PCNA expression by activating Akt\/mTOR, leading to abnormal cell proliferation. Conversely, in endothelial cells, elevated S1PR2 expression reduced VE\u2010cadherin expression by activating the RhoA\/ROCK1 pathway, increasing endothelial permeability. In an apolipoprotein E\u2010deficient mouse model, S1PR2 agonist treatment reduced the abnormal proliferation of aortic smooth muscle cells, while S1PR2 antagonist treatment alleviated barrier function damage in aortic endothelial cells. However, both S1PR2 agonist and antagonist treatments showed limited efficacy on aortic plaques due to their opposing effects on endothelial cells and smooth muscle cells. Thus, therapies targeting specific cell types hold significant promise, and S1PR2 may be a potential target for the prevention and treatment of atherosclerosis.<\/jats:p>","DOI":"10.1002\/jbt.70351","type":"journal-article","created":{"date-parts":[[2025,6,11]],"date-time":"2025-06-11T04:01:36Z","timestamp":1749614496000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["S1PR2 Mediates Smooth Muscle Cell Proliferation and Endothelial Cell Permeability via Akt\/mTOR and RhoA\/ROCK1 in Atherosclerosis"],"prefix":"10.1002","volume":"39","author":[{"given":"Jie","family":"Ouyang","sequence":"first","affiliation":[{"name":"Health Management Center the Third Xiangya Hospital of Central South University Changsha China"},{"name":"Department of Cardiology the Third Xiangya Hospital of Central South University Changsha 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