{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T06:27:56Z","timestamp":1777530476713,"version":"3.51.4"},"reference-count":44,"publisher":"SAGE Publications","issue":"6","license":[{"start":{"date-parts":[[2018,5,20]],"date-time":"2018-05-20T00:00:00Z","timestamp":1526774400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"name":"Sociedade Brasileira de Cardiologia - SBC","award":["2014\/03742-0"],"award-info":[{"award-number":["2014\/03742-0"]}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["J Cardiovasc Pharmacol Ther"],"published-print":{"date-parts":[[2018,11]]},"abstract":"<jats:p>In previous studies, it was demonstrated that lipid core nanoparticles (LDE) resemble the low-density lipoprotein structure and carrying the antiproliferative agent paclitaxel (PTX) strongly reduced atherosclerosis lesions induced in rabbits by cholesterol feeding. Currently, the aim was to verify whether combining LDE-PTX treatment with methotrexate (MTX) associated with LDE (LDE-MTX) could accelerate the atherosclerosis regression attained with single LDE-PTX treatment, after withdrawing the cholesterol feeding. Thirty-eight rabbits were fed 1% cholesterol chow for 8 weeks. Six of these rabbits were then euthanized for analyses of the aorta (controls). In the remaining rabbits, cholesterol feeding was withdrawn, and those 32 animals were allocated to 3 groups submitted to different 8-week intravenous treatments, all once\/week: LDE-PTX (n = 10; 4 mg\/kg), LDE-PTX + LDE-MTX (n = 11; 4 mg\/kg), and LDE-alone (n = 11). Rabbits were then euthanized and aortas were excised for morphometric, immunohistochemical, and gene expression analyses. After cholesterol feeding withdrawal, in comparison with LDE-alone group, both LDE-PTX and LDE-PTX + LDE-MTX treatments had the ability to increase the regression of plaque areas: \u221249% in LDE-PTX and \u221259% for LDE-PTX + LDE-MTX. However, only LDE-PTX + LDE-MTX treatment elicited reduction in the intima area, estimated in \u221257%. Macrophage presence in aortic lesions was reduced 48% by LDE-PTX and 43% by LDE-PTX + LDE-MTX treatment. Matrix metalloproteinase 9 was reduced by either LDE-PTX (74%) or LDE-PTX + LDE-MTX (78%). Tumor necrosis factor \u03b1 gene expression was reduced 65% by LDE-PTX and 79% by LDE-PTX + LDE-MTX. In conclusion, treatment with LDE-PTX indeed accelerated plaque reduction after cholesterol feeding; LDE-PTX + LDE-MTX further increased this effect, without any observed toxicity. These results pave the way for the use of combined chemotherapy to achieve stronger effects on aggravated, highly inflamed atherosclerotic lesions.<\/jats:p>","DOI":"10.1177\/1074248418778836","type":"journal-article","created":{"date-parts":[[2018,5,20]],"date-time":"2018-05-20T23:22:29Z","timestamp":1526858549000},"page":"561-569","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":38,"title":["Regression of Atherosclerotic Plaques of Cholesterol-Fed Rabbits by Combined Chemotherapy With Paclitaxel and Methotrexate Carried in Lipid Core Nanoparticles"],"prefix":"10.1177","volume":"23","author":[{"given":"Fernando L. 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