{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T15:38:57Z","timestamp":1791041937102,"version":"4.1.0"},"reference-count":28,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"9","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["ATVB"],"published-print":{"date-parts":[[2010,9]]},"abstract":"<jats:p>\n            <jats:bold>\n              <jats:italic>Objective\u2014<\/jats:italic>\n            <\/jats:bold>\n            To assess the role of combined deficiencies of vitamins C and E on the earliest stages of atherosclerosis (an inflammatory condition associated with oxidative stress), 4 combinations of vitamin supplementation (low C\/low E, low C\/high E, high C\/low E, and high C\/high E) were studied in atherosclerosis-prone apolipoprotein E\u2013deficient mice also unable to synthesize their own vitamin C (gulonolactone oxidase\n            <jats:sup>\u2212\/\u2212<\/jats:sup>\n            ); and to evaluate the effect of a more severe depletion of vitamin C alone in a second experiment using gulonolactone oxidase\n            <jats:sup>\u2212\/\u2212<\/jats:sup>\n            mice carrying the hemizygous deletion of SVCT2 (the vitamin C transporter).\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>\n              <jats:italic>Methods and Results\u2014<\/jats:italic>\n            <\/jats:bold>\n            After 8 weeks of a high-fat diet (16% lard and 0.2% cholesterol), atherosclerosis developed in the aortic sinus areas of mice in all diet groups. Each vitamin-deficient diet significantly decreased liver and brain contents of the corresponding vitamin. Combined deficiency of both vitamins increased lipid peroxidation, doubled plaque size, and increased plaque macrophage content by 2- to 3-fold in male mice, although only plaque macrophage content was increased in female mice. A more severe deficiency of vitamin C in gulonolactone oxidase\n            <jats:sup>\u2212\/\u2212<\/jats:sup>\n            mice with defective cellular uptake of vitamin C increased both oxidative stress and atherosclerosis in apolipoprotein E\n            <jats:sup>\u2212\/\u2212<\/jats:sup>\n            mice compared with littermates receiving a diet replete in vitamin C, again most clearly in males.\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>\n              <jats:italic>Conclusion\u2014<\/jats:italic>\n            <\/jats:bold>\n            Combined deficiencies of vitamins E and C are required to worsen early atherosclerosis in an apolipoprotein E\u2013deficient mouse model. However, a more severe cellular deficiency of vitamin C alone promotes atherosclerosis when vitamin E is replete.\n          <\/jats:p>","DOI":"10.1161\/atvbaha.110.209502","type":"journal-article","created":{"date-parts":[[2010,6,18]],"date-time":"2010-06-18T02:53:23Z","timestamp":1276829603000},"page":"1751-1757","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":32,"title":["Combined Vitamin C and Vitamin E Deficiency Worsens Early Atherosclerosis in Apolipoprotein E\u2013Deficient Mice"],"prefix":"10.1161","volume":"30","author":[{"given":"Vladimir R.","family":"Babaev","sequence":"first","affiliation":[{"name":"From the Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tenn."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liying","family":"Li","sequence":"additional","affiliation":[{"name":"From the Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tenn."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanket","family":"Shah","sequence":"additional","affiliation":[{"name":"From the Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tenn."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergio","family":"Fazio","sequence":"additional","affiliation":[{"name":"From the Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tenn."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"MacRae F.","family":"Linton","sequence":"additional","affiliation":[{"name":"From the Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tenn."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James M.","family":"May","sequence":"additional","affiliation":[{"name":"From the Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tenn."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199901143400207"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1001\/archinte.167.15.1610"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(02)09328-5"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2008.600"},{"key":"e_1_3_3_5_2","first-page":"17","volume":"69","year":"1953","unstructured":"Willis GC. 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