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Rodent models that capture these early events are needed for mechanistic and interventional studies. This study evaluated whether a cholesterol\u2010rich, high\u2010fat diet (HFD) supplemented with vitamin D and propylthiouracil (PTU) promotes a pro\u2010atherogenic phenotype in rats, as evidenced by dyslipidemia, inflammation, markers of endothelial dysfunction, and early vascular remodeling.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Male Sprague\u2013Dawley rats (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200918) received standard chow or a HFD containing 2% cholesterol, 3% lard, 0.5% cholate, vitamin D (200 000\u2009IU\/kg), and PTU (0.2% w\/w) for 11\u2009weeks. Terminal serum total cholesterol, high\u2010density lipoprotein, low\u2010density lipoprotein (LDL)\/very low\u2010density lipoprotein (VLDL), triglycerides, calcium, interleukin\u20106 (IL\u20106), C\u2010reactive protein, serum amyloid A (SAA), circulating endothelial nitric oxide synthase (eNOS), and intracellular adhesion molecule\u20101 (ICAM\u20101) were measured. The aorta, the coronary arteries, and the liver were examined histologically.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      HFD\u2010fed rats developed significant hypercholesterolemia with higher total cholesterol and LDL\/VLDL (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.0001) and lower triglycerides (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.0001) versus controls. Serum calcium was higher (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.0001) without vascular calcification. Aortae exhibited wall thickening, smooth\u2010muscle disarray, mononuclear infiltrates, and focal foam cell\u2010like changes; coronary arteries exhibited endothelial irregularities and perivascular infiltrates. Livers exhibited micro\u2010 and macrovesicular steatosis. IL\u20106 and SAA were higher (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.05), and circulating eNOS was lower (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.05); ICAM\u20101 did not differ significantly.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>An 11\u2010week vitamin D\/PTU\u2010supplemented HFD induces an LDL\u2010dominant dyslipidemia with systemic inflammation and evidence consistent with endothelial dysfunction, alongside histological features of early vascular remodeling and hepatic steatosis. This nongenetic model may be useful for studying early atherogenic changes.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ame2.70178","type":"journal-article","created":{"date-parts":[[2026,4,2]],"date-time":"2026-04-02T04:27:41Z","timestamp":1775104061000},"page":"1026-1036","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A high\u2010fat diet with vitamin D and propylthiouracil produces a pro\u2010atherogenic phenotype in rats"],"prefix":"10.1002","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5624-1386","authenticated-orcid":false,"given":"Ang\u00e9lique","family":"Lewies","sequence":"first","affiliation":[{"name":"Department of Cardiothoracic Surgery, Robert WM Frater Cardiovascular Research Centre, Faculty of Health Sciences University of the Free State  Bloemfontein South 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