{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,7]],"date-time":"2026-03-07T02:56:08Z","timestamp":1772852168531,"version":"3.50.1"},"reference-count":126,"publisher":"Public Library of Science (PLoS)","issue":"2","license":[{"start":{"date-parts":[[2021,2,24]],"date-time":"2021-02-24T00:00:00Z","timestamp":1614124800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100005191","name":"Craig H. Neilsen Foundation","doi-asserted-by":"publisher","award":["340428"],"award-info":[{"award-number":["340428"]}],"id":[{"id":"10.13039\/100005191","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"\nObjective<\/jats:title>\nTo test in mice with a double mutation of the ApoE gene (ApoE<\/jats:italic>-\/-<\/jats:italic><\/jats:sup>) whether spinal cord injury (SCI) hastens the native trajectory of, and established component risks for, atherosclerotic disease (AD), and whether Salsalate anti-inflammatory pharmacotherapy attenuates the impact of SCI.<\/jats:p>\n<\/jats:sec>\n\nMethods<\/jats:title>\nApoE<\/jats:italic>-\/-<\/jats:italic><\/jats:sup> mice were anesthetized and underwent a T9 laminectomy. Exposed spinal cords were given a contusion injury (70 k-dynes). Sham animals underwent all surgical procedures, excluding injury. Injured animals were randomized to 2 groups: SCI or SCI+Salsalate<\/jats:sub> [120 mg\/Kg\/day i.p.]. Mice were serially sacrificed at 20-, 24-, and 28-weeks post-SCI, and body mass was recorded. At sacrifice, heart and aorta were harvested intact, fixed in 10% buffered formalin, cleaned and cut longitudinally for en face<\/jats:italic> preparation. The aortic tree was stained with oil-red-O (ORO). AD lesion histomorphometry was calculated from the proportional area of ORO. Plasma total cholesterol, triglycerides and proatherogenic inflammatory cytokines (PAIC\u2019s) were analyzed.<\/jats:p>\n<\/jats:sec>\n\nResults<\/jats:title>\nAD lesion in the aortic arch progressively increased in ApoE<\/jats:italic>-\/-<\/jats:italic><\/jats:sup>, significant at 24- and 28-weeks. AD in SCI is significantly greater at 24- and 28-weeks compared to time-controlled ApoE<\/jats:italic>-\/-<\/jats:italic><\/jats:sup>. Salsalate treatment attenuates the SCI-induced increase at these time points. Body mass in all SCI groups are significantly reduced compared to time-controlled ApoE<\/jats:italic>-\/-<\/jats:italic><\/jats:sup>. Cholesterol and triglycerides are significantly higher with SCI by 24- and 28-weeks, compared to ApoE<\/jats:italic>-\/-<\/jats:italic><\/jats:sup>, and Salsalate reduces the SCI-induced effect on cholesterol. PAIC\u2019s interleukin-1\u03b2 (IL-1\u03b2), interleukin-6 (IL-6), tumor necrosis factor \u03b1 (TNF\u03b1), monocyte chemoattractant protein-1 (MCP-1), and chemokine (C-C motif) ligand 5 (CCL-5) are significantly greater with SCI compared to ApoE<\/jats:italic>-\/-<\/jats:italic><\/jats:sup> at varying timepoints. Salsalate confers a marginal reducing effect on PAIC\u2019s by 28-weeks compared to SCI. Regression models determine that each PAIC is a significant and positive predictor of lesion. (p\u2019s <0.05).<\/jats:p>\n<\/jats:sec>\n\nConclusions<\/jats:title>\nSCI accelerates aortic AD and associated risk factors, and anti-inflammatory treatment may attenuate the impact of SCI on AD outcomes. PAIC\u2019s IL-1\u03b2, IL-6, TNF\u03b1, MCP-1, and CCL-5 may be effective predictors of AD.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0246601","type":"journal-article","created":{"date-parts":[[2021,2,24]],"date-time":"2021-02-24T18:30:21Z","timestamp":1614191421000},"page":"e0246601","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":7,"title":["Cardiometabolic risks and atherosclerotic disease in ApoE knockout mice: Effect of spinal cord injury and Salsalate anti-inflammatory pharmacotherapy"],"prefix":"10.1371","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8990-3465","authenticated-orcid":true,"given":"Gregory 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