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

Area of Science:

• Cardiovascular Research
• Immunology
• Pharmacology

Background:

• Toll-like receptor 4 (TLR4) plays a key role in atherosclerosis development.
• The therapeutic potential of TLR4 inhibitors in attenuating atherosclerosis remains unclear.

Purpose of the Study:

• To investigate the vascular protective effects of the TLR4 inhibitor CLI-095.
• To evaluate CLI-095's impact on atherosclerosis in apolipoprotein E-deficient (ApoE-/-) mice.

Main Methods:

• ApoE-/- mice were fed a high-fat diet and treated with or without CLI-095 for 10 weeks.
• In vitro studies involved stimulating murine peritoneal macrophages with oxidized low-density lipoprotein (oxLDL) in the presence or absence of CLI-095.
• Key molecular markers of foam cell formation and cholesterol efflux were assessed.

Main Results:

• CLI-095 treatment reduced mean atherosclerotic plaque area by 54.3% in vivo.
• In vitro, CLI-095 decreased lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) and acyl-coenzyme A:cholesterol acyltransferase-1 (ACAT-1) expression.
• CLI-095 upregulated ATP-binding cassette transporter A1 (ABCA1) expression, suppressing TLR4/nuclear factor-κB (NF-κB) signaling.

Conclusions:

• The TLR4 inhibitor CLI-095 demonstrates significant potential in suppressing atherosclerosis progression.
• CLI-095 mitigates atherosclerosis by reducing macrophage foam cell formation via the TLR4/NF-κB pathway.