Atherosclerosis is a chronic inflammatory cardiovascular disease with high 
mortality worldwide. Tofacitinib (CP-690,550), an oral small-molecule Janus 
kinase inhibitor, has been shown to be effective in the treatment of rheumatoid 
arthritis, autoimmune encephalomyelitis and ulcerative colitis. However, its 
protective effect against atherosclerosis remains poorly understood. The aim of 
the present study was to evaluate the effects of Tofacitinib on atherogenic diet 
(ATD)-induced atherosclerosis using apolipoprotein E deficient (apoE-/-) mice. 
Atherosclerosis-prone apoE-/- mice were fed with ATD and treated with or without 
Tofacitinib through intragastrical administration (10 mg kg-1 day-1) for 8 
weeks. Our results showed that Tofacitinib did not change plasma lipids, while 
significantly reduced the levels of plasma pro-inflammatory cytokines IL-6 and 
TNF-α. It also significantly attenuated atherosclerotic plaque lesion in the 
aortic root and macrophages contained in plaque as shown with Mac2 
immuno-staining. Peritoneal macrophages (PMC) were separated from apoE-/- mice 
fed with 8-week ATD, and then subjected to inflammation tests. Flow cytometry 
analysis of F4/80 and CD206 and mRNA levels of M1 and M2 macrophages markers 
showed that M1 macrophages decreased while M2 macrophages increased in 
Tofacitinib treated group. Expressions of other inflammatory genes also 
indicated an anti-inflammatory status in mice treated with Tofacitinib. Ox-LDL 
was used to induce foam cell formation from PMC in wild type mice, and the 
results displayed a reduced formation of foam cells and decreased inflammation 
in mice with Tofacitinib administration (1 μM). The mRNA and protein levels of 
ATP binding cassette subfamily A member 1 (ABCA1), a key gene involved in 
cholesterol efflux, remarkably increased, while it was absence of alterations in 
scavenger receptors expression. Therefore, we demonstrated that Tofacitinib 
could attenuate atherosclerosis and foam cells formation by inhibiting 
inflammation and upregulating ABCA1 expression.