KLF4 Upregulation in Atherosclerotic Thoracic Aortas: Exploring the Protective Effect of Colchicine-based Regimens in a Hyperlipidemic Rabbit Model.
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 four 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 seven weeks, all animals were euthanized, and their thoracic aortas were isolated. Atherosclerotic plaque area was estimated with morphometric analysis. KLF4 expression was quantified with qRT-PCR.Group A developed significantly more atherosclerosis compared to group B (MD: 13.67, 95% CI: 7.49 to 19.84) and C (MD: 20.29, 95% CI: 14.12 to 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.
Authors: Konstantinos S Mylonas, Alkistis Kapelouzou, Michael Spartalis, Michael Mastrogeorgiou, Eletherios Spartalis, Christos Bakoyiannis, Theodoros Liakakos, Dimitrios Schizas, Dimitrios Iliopoulos, Nikolaos Nikiteas