Journal
MOLECULAR MEDICINE REPORTS
Volume 14, Issue 1, Pages 49-56Publisher
SPANDIDOS PUBL LTD
DOI: 10.3892/mmr.2016.5233
Keywords
toll-like receptor 4; CLI-095; foam cell; atherosclerosis; macrophage
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Funding
- Second Affiliated Hospital of Dalian Medical University
- National Natural Science Foundation of China [81372853]
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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 E-deficient (ApoE(-/-)) mice. ApoE(-/-) ice were fed either chow or a high-fat diet, and were treated with or without CLI-095 for 10 weeks. The mean atherosclerotic plaque area in the aortic sections of CLI-095-treated mice was 54.3% smaller than in the vehicle-treated mice (P=0.0051). In vitro, murine peritoneal macrophages were treated with or without CLI-095, and were subsequently stimulated with oxidized low-density lipoprotein. Treatment with CLI-095 markedly reduced the expression levels of lectin-like oxidized low-density lipoprotein receptor-1 and acylcoen-zyme A: cholesterol acyltransferase-1, and significantly upregulated the expression levels of ATP-binding cassette transporter A1, predominantly via suppressing activation of the TLR4/nuclear factor-kappa B signaling pathway. The results of the present study indicated that the TLR4 inhibitor CLI-095 has the ability to suppress the progression of atherosclerosis in an in vivo model by reducing macrophage foam cell formation.
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