CLI-095 decreases atherosclerosis by modulating foam cell formation in apolipoprotein E-deficient mice.

Toll-like receptor 4 (TLR4) is considered to have a critical role in the occurrence and development of atherosclerosis in atherosclerosis-prone mice; however, it remains uncertain whether treatment with a TLR4 inhibitor may attenuate atherosclerosis. The present study aimed to determine the vascular protective effects of the TLR4 inhibitor CLI-095 on apolipoprotein E­deficient (ApoE­/­) mice. ApoE­/­ mice were fed either chow or a high­fat diet, and were treated with or without CLI­095 for 10 weeks. The mean atherosclerotic plaque area in the aortic sections of CLI­095­treated mice was 54.3% smaller than in the vehicle­treated mice (P=0.0051). In vitro, murine peritoneal macrophages were treated with or without CLI­095, and were subsequently stimulated with oxidized low­density lipoprotein. Treatment with CLI­095 markedly reduced the expression levels of lectin­like oxidized low­density lipoprotein receptor­1 and acyl-coenzyme A:cholesterol acyltransferase­1, and significantly upregulated the expression levels of ATP­binding cassette transporter A1, predominantly via suppressing activation of the TLR4/nuclear factor­κB signaling pathway. The results of the present study indicated that the TLR4 inhibitor CLI­095 has the ability to suppress the progression of atherosclerosis in an in vivo model by reducing macrophage foam cell formation.