1. Effects of edoxaban and warfarin on vascular remodeling: Atherosclerotic plaque progression and collateral artery growth.
- Author
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Millenaar D, Bachmann P, Böhm M, Custodis F, and Schirmer SH
- Subjects
- Animals, Atherosclerosis pathology, Atherosclerosis physiopathology, Disease Models, Animal, Fibrosis, Hindlimb, Ischemia physiopathology, Mice, Inbred C57BL, Mice, Knockout, ApoE, Anticoagulants pharmacology, Atherosclerosis drug therapy, Collateral Circulation drug effects, Factor Xa Inhibitors pharmacology, Ischemia drug therapy, Muscle, Skeletal blood supply, Neovascularization, Physiologic drug effects, Plaque, Atherosclerotic, Pyridines pharmacology, Thiazoles pharmacology, Vascular Remodeling drug effects, Warfarin pharmacology
- Abstract
Background and Purpose: Oral anticoagulation prevents thromboembolism in atrial fibrillation. Factor Xa inhibitors, like edoxaban, are known to reduce inflammation and proliferation of smooth muscle cells, while vitamin K antagonism can cause vascular calcific damage. The influence of edoxaban compared to warfarin on vascular remodeling, atherosclerosis and arteriogenesis is unknown., Experimental Approach: Apolipoprotein E knockout (ApoE
-/- ) mice were fed cholesterol-rich diet alone (control, co), with warfarin+vitamin K1 (warf) or with edoxaban (Edo) for 8 weeks. After 6 weeks, femoral artery ligation was performed., Key Results: There was no difference in hind-limb perfusion restoration between the three groups after 14 days (Co 0.36 ± 0.05 vs. Warf 0.39 ± 0.09 (p = .39), Co vs. Edo 0.51 ± 0.06 (p = .089), Warf vs. Edo (p = .83)) after ligation. Immuno-histologically, there was no difference in smooth muscle cell count in both hindlimbs between the three groups or in the amount of perivascular macrophages in collateral-bearing hindlimb tissue. Edoxaban showed the lowest amount of plaque tissue in the aortic sinus tissue (Co 74 ± 11% vs. Edo 62 ± 12% (p = .024), Co vs. Warf 69 ± 14% (p = .30), Edo vs. Warf (p = .14)) as well as the least amount of fibrosis (Co 3.1 ± 0.9% vs. Edo 1.7 ± 0.6% (p = .027), Co vs. Warf 4.1 ± 0.7% (p = .081), Edo vs. Warf (p < .001)). No difference in mRNA content of inflammatory cytokines in muscle tissue or spleen was detected between the three groups., Conclusion and Implications: These data suggest that treatment with edoxaban unlike warfarin prevents vascular maladaptive remodeling, which may be clinically important., Competing Interests: Declaration of Competing Interest DM has received lecture/consulting fees from Bayer and Daiichi Sankyo and research funding from Daiichi Sankyo. MB and SHS have received lecture fees and/or research funding from Boehringer Ingelheim, Bayer, Daiichi Sankyo, BMS, Pfizer, Medtronic, Abbott, Astra Zeneca, Servier, Amgen. PB and FC have no disclosures., (Copyright © 2020 Elsevier Inc. All rights reserved.)- Published
- 2020
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