Τίτλος:
KLF4 Upregulation in Atherosclerotic Thoracic Aortas: Exploring the Protective Effect of Colchicine-based Regimens in a Hyperlipidemic Rabbit Model
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
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
Συγγραφείς:
Mylonas, K.S.
Kapelouzou, A.
Spartalis, M.
Mastrogeorgiou, M.
Spartalis, E.
Bakoyiannis, C.
Liakakos, T.
Schizas, D.
Iliopoulos, D.
Nikiteas, N.
Περιοδικό:
Annals of Vascular Surgery
Εκδότης:
HANLEY & BELFUS-ELSEVIER INC
Λέξεις-κλειδιά:
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
DOI:
10.1016/j.avsg.2021.04.040
