A high-fat diet with vitamin D and propylthiouracil produces a pro-atherogenic phenotype in ratsOA

Background:Atherosclerosis begins with dyslipidemia,vascular inflammation,and en-dothelial dysfunction.Rodent models that capture these early events are needed for mechanistic and interventional studies.This study evaluated whether a cholesterol-rich,high-fat diet(HFD)supplemented with vitamin D and propylthiouracil(PTU)promotes a pro-atherogenic phenotype in rats,as evidenced by dyslipidemia,inflam-mation,markers of endothelial dysfunction,and early vascular remodeling.Methods:Male Sprague-Dawley rats(n=18)received standard chow or a HFD con-taining 2%cholesterol,3%lard,0.5%cholate,vitamin D(200000 IU/kg),and PTU(0.2%w/w)for 11 weeks.Terminal serum total cholesterol,high-density lipoprotein,low-density lipoprotein(LDL)/very low-density lipoprotein(VLDL),triglycerides,calcium,interleukin-6(IL-6),C-reactive protein,serum amyloid A(SAA),circulating endothelial nitric oxide synthase(eNOS),and intracellular adhesion molecule-1(ICAM-1)were measured.The aorta,the coronary arteries,and the liver were examined histologically.Results:HFD-fed rats developed significant hypercholesterolemia with higher total cholesterol and LDL/VLDL(p<0.0001)and lower triglycerides(p<0.0001)versus controls.Serum calcium was higher(p<0.0001)without vascular calcification.Aortae exhibited wall thickening,smooth-muscle disarray,mononuclear infiltrates,and focal foam cell-like changes;coronary arteries exhibited endothelial irregularities and perivascular infiltrates.Livers exhibited micro-and macrovesicular steatosis.IL-6 and SAA were higher(p<0.05),and circulating eNOS was lower(p<0.05);ICAM-1 did not differ significantly.Conclusion:An 11-week vitamin D/PTU-supplemented HFD induces an LDL-dominant 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.