BackgroundChronic inflammation is a key player in the process of atherosclerosis. The present study was designed to investigate effects of immunosuppressive agents on endothelial dysfunction in a mouse model of atherosclerosis.MethodsTo induce atherosclerosis, 6‐week old LDLR knockout mice were fed with western diet for two months. Clinically used immunosuppressive agents, cyclosporine and mycophenolate, were mixed in chow. Aortic rings were fixed in the organ chambers for isometric tension measurement. Atherosclerotic plaques in aortic arch were visualized using Oil red O (ORO) staining and the level of CD68, COX‐2 positive cells was studied by Immunofluorescence. Lipoprotein and creatinine levels was measured using serum.Key resultsORO staining showed that atherosclerosis plaques in the aortic arch were reduced in mice fed with immunosuppressive drugs, compared with those fed with western diet. Acetylcholine induced relaxations at low concentrations, but contractions at high concentrations in the aorta of LDLR knockout mice. The acetylcholine‐induced contractions, but not the relaxations, were significantly reduced in mice treated with immunosuppressive agents. In the presence of indomethacin (non‐selective inhibitor of cyclooxygenase), acetylcholine‐induced contractions were restored to relaxations in both groups. The CD68, COX‐2 positive cells in the plaques of the two groups were not significantly different. In addition, there was no significant difference in serum lipoprotein and creatinine levels between the two groups of mice.ConclusionImmunosuppressive treatment reduces atherosclerotic plaque and prevents endothelial dysfunction in LDLR knockout mice. The underlying mechanisms may involve cyclooxygenase pathway; further studies are warranted to confirm, or not, the postulation.Support or Funding InformationThe present study was supported by the National Nature Science Foundation of China (81573418) and ZSYXRC‐014This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.