KLF4 Upregulation in Atherosclerotic Thoracic Aortas: Exploring the Protective Effect of Colchicine-based Regimens in a Hyperlipidemic Rabbit Model

•Rabbits were fed regular or hyperlipidemic diets ± colchicine-based regimens.•KLF4 was upregulated in the thoracic aortas of all hyperlipidemic groups.•Smaller plaques were found when combining NAC with colchicine instead of fibrate.•Less KLF4 upregulation was noted in the colchicine plus N-acetylcysteine group.•Colchicine-based regimens curtailed de novo atherogenesis and KLF4 expression. Inflammatory dysregulation of KLF4 is related to atheromatosis. In the present study, we explored the impact of colchicine-based regimens on the development of thoracic aortic atheromatosis and KLF4 expression. Twenty-eight New Zealand White rabbits were divided to 4 groups. The control group (n = 6) was fed standard chow, group A (n = 6) was fed chow enriched with 1% w/w cholesterol, group B (n = 8) was fed the same cholesterol-enriched diet plus 2 mg/kg body weight/day colchicine and 250 mg/kg body weight/day fenofibrate, while group C (n = 8) was also fed the same diet plus 2 mg/kg body weight/day colchicine and 15 mg/kg body weight/day N-acetylcysteine. After 7 weeks, all animals were euthanized, and their thoracic aortas were isolated. Atherosclerotic plaque area was estimated with morphometric analysis. KLF4 expression was quantified with quantitative RT-PCR. Group A developed significantly more atherosclerosis compared to group B (MD: 13.67, 95% CI: 7.49–19.84) and C (MD: 20.29, 95% CI: 14.12–26.47). Colchicine with N-acetylcysteine resulted in more pronounced reduction in the extent of atherosclerotic plaques compared to colchicine/fibrate (MD: 6.62, 95% CI: 0.90–12.34). Group A exhibited significantly greater KLF4 expression compared to group B (MD: 4.94, 95% CI: 1.11–8.77) and C (MD: 9.94, 95% CI: 6.11–13.77). Combining colchicine with N-acetylcysteine instead of fenofibrate (MD: 5.00, 95% CI: 1.45–8.54) led to a more robust reduction in KLF4 expression. In the present hyperlipidemic animal model, colchicine-based regimens curtailed de novo atherogenesis and KLF4 overexpression in thoracic aortas.