@article{3118839,
    title = "KLF4 Upregulation in Atherosclerotic Thoracic Aortas: Exploring the Protective Effect of Colchicine-based Regimens in a Hyperlipidemic Rabbit Model",
    author = "Mylonas, K.S. and Kapelouzou, A. and Spartalis, M. and Mastrogeorgiou, M. and Spartalis, E. and Bakoyiannis, C. and Liakakos, T. and Schizas, D. and Iliopoulos, D. and Nikiteas, N.",
    journal = "Annals of Vascular Surgery",
    year = "2022",
    volume = "78",
    pages = "328-335",
    publisher = "HANLEY & BELFUS-ELSEVIER INC",
    issn = "0890-5096",
    doi = "10.1016/j.avsg.2021.04.040",
    keywords = "acetylcysteine;  cholesterol;  colchicine;  fenofibrate;  kruppel like factor 4;  acetylcysteine;  antiinflammatory agent;  colchicine;  fibric acid derivative, animal experiment;  animal model;  animal tissue;  antiinflammatory activity;  aortic atherosclerosis;  Article;  atherogenic diet;  atheromatous plaque;  body weight;  cell proliferation;  chow diet;  controlled study;  drug effect;  fatty streak;  histopathology;  hyperlipidemia;  male;  New Zealand White (rabbit);  nonhuman;  protein expression;  rabbit model;  thoracic aorta;  upregulation;  animal;  aortic disease;  atherosclerosis;  atherosclerotic plaque;  combination drug therapy;  comparative study;  complication;  disease model;  drug effect;  genetics;  hyperlipidemia;  Leporidae;  metabolism;  pathology;  thoracic aorta;  upregulation, Acetylcysteine;  Animals;  Anti-Inflammatory Agents;  Aorta, Thoracic;  Aortic Diseases;  Atherosclerosis;  Colchicine;  Disease Models, Animal;  Drug Therapy, Combination;  Fibric Acids;  Hyperlipidemias;  Kruppel-Like Factor 4;  Male;  Plaque, Atherosclerotic;  Rabbits;  Up-Regulation",
    abstract = "Background: 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. Methods: 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. Results: 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. Conclusions: In the present hyperlipidemic animal model, colchicine-based regimens curtailed de novo atherogenesis and KLF4 overexpression in thoracic aortas. © 2021"
}