{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T05:00:07Z","timestamp":1787029207678,"version":"build-2736575974"},"reference-count":98,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2023,4,28]],"date-time":"2023-04-28T00:00:00Z","timestamp":1682640000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81573143"],"award-info":[{"award-number":["81573143"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81872612"],"award-info":[{"award-number":["81872612"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Sulforaphane (SFN), an isothiocyanate, is one of the major dietary phytochemicals found in cruciferous vegetables. Many studies suggest that SFN can protect against cancer and cardiometabolic diseases. Despite the proposed systemic and local vascular protective mechanisms, SFN\u2019s potential to inhibit atherogenesis by targeting macrophages remains unknown. In this study, in high fat diet fed ApoE-deficient (ApoE\u2212\/\u2212) mice, oral SFN treatment improved dyslipidemia and inhibited atherosclerotic plaque formation and the unstable phenotype, as demonstrated by reductions in the lesion areas in both the aortic sinus and whole aorta, percentages of necrotic cores, vascular macrophage infiltration and reactive oxygen species (ROS) generation. In THP-1-derived macrophages, preadministration SFN alleviated oxidized low-density lipoprotein (ox-LDL)-induced lipid accumulation, oxidative stress and mitochondrial injury. Moreover, a functional study revealed that peritoneal macrophages isolated from SFN-treated mice exhibited attenuated cholesterol influx and enhanced apolipoprotein A-I (apoA-I)- and high-density lipoprotein (HDL)-mediated cholesterol efflux. Mechanistic analysis revealed that SFN supplementation induced both intralesional and intraperitoneal macrophage phenotypic switching toward high expression of nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1) and ATP-binding cassette subfamily A\/G member 1 (ABCA1\/G1) and low expression of peroxisome proliferator-activated receptor \u03b3 (PPAR\u03b3) and cluster of differentiation 36 (CD36), which was further validated by the aortic protein expression. These results suggest that the regulation of macrophages\u2019 cholesterol transport and accumulation may be mainly responsible for SFN\u2019s potential atheroprotective properties, and the regulatory mechanisms might involve upregulating ABCA1\/G1 and downregulating CD36 via the modulation of PPAR\u03b3 and Nrf2.<\/jats:p>","DOI":"10.3390\/nu15092117","type":"journal-article","created":{"date-parts":[[2023,4,28]],"date-time":"2023-04-28T02:27:56Z","timestamp":1682648876000},"page":"2117","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Sulforaphane Inhibits Foam Cell Formation and Atherosclerosis via Mechanisms Involving the Modulation of Macrophage Cholesterol Transport and the Related Phenotype"],"prefix":"10.3390","volume":"15","author":[{"given":"Shiyan","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Nutrition, School of Public Health, Sun Yat-sen University, Guangzhou 510080, China"},{"name":"Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Guangzhou 510080, China"},{"name":"Guangdong Engineering Technology Center of Nutrition Transformation, Guangzhou 510080, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Geriatrics, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou 510150, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiangyu","family":"Zheng","sequence":"additional","affiliation":[{"name":"Department of Nutrition, School of Public Health, Sun Yat-sen University, Guangzhou 510080, China"},{"name":"Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Guangzhou 510080, China"},{"name":"Guangdong Engineering Technology Center of Nutrition Transformation, Guangzhou 510080, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziling","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Nutrition, School of Public Health, Sun Yat-sen University, Guangzhou 510080, China"},{"name":"Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Guangzhou 510080, China"},{"name":"Guangdong Engineering Technology Center of Nutrition Transformation, Guangzhou 510080, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pan","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Nutrition, School of Public Health, Sun Yat-sen University, Guangzhou 510080, China"},{"name":"Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Guangzhou 510080, China"},{"name":"Guangdong Engineering Technology Center of Nutrition Transformation, Guangzhou 510080, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengdi","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Nutrition, School of Public Health, Sun Yat-sen University, Guangzhou 510080, China"},{"name":"Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Guangzhou 510080, China"},{"name":"Guangdong Engineering Technology Center of Nutrition Transformation, Guangzhou 510080, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengfan","family":"Shen","sequence":"additional","affiliation":[{"name":"Department of Nutrition, School of Public Health, Sun Yat-sen University, Guangzhou 510080, China"},{"name":"Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Guangzhou 510080, China"},{"name":"Guangdong Engineering Technology Center of Nutrition Transformation, Guangzhou 510080, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6425-0370","authenticated-orcid":false,"given":"Yongping","family":"Bao","sequence":"additional","affiliation":[{"name":"Norwich Medical School, University of East Anglia, Norwich NR4 7UQ, Norfolk, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6458-6096","authenticated-orcid":false,"given":"Dan","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Nutrition, School of Public Health, Sun Yat-sen University, Guangzhou 510080, China"},{"name":"Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Guangzhou 510080, China"},{"name":"Guangdong Engineering Technology Center of Nutrition Transformation, Guangzhou 510080, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,4,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1038\/nri3520","article-title":"Macrophages in atherosclerosis: A dynamic balance","volume":"13","author":"Moore","year":"2013","journal-title":"Nat. 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