1. Decreased M1 macrophage polarization in dabigatran-treated Ldlr-deficient mice: Implications for atherosclerosis and adipose tissue inflammation.
- Author
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Feldmann K, Grandoch M, Kohlmorgen C, Valentin B, Gerfer S, Nagy N, Hartwig S, Lehr S, Fender AC, and Fischer JW
- Subjects
- Adipose Tissue drug effects, Adipose Tissue metabolism, Animals, Antithrombins pharmacology, Aorta, Thoracic drug effects, Aorta, Thoracic metabolism, Atherosclerosis metabolism, Atherosclerosis pathology, Disease Models, Animal, Female, Flow Cytometry, Immunohistochemistry, Inflammation metabolism, Inflammation pathology, Macrophages metabolism, Mice, Mice, Inbred C57BL, Mice, Knockout, Adipose Tissue pathology, Aorta, Thoracic pathology, Atherosclerosis drug therapy, Dabigatran pharmacology, Inflammation drug therapy, Macrophage Activation physiology, Macrophages pathology
- Abstract
Background and Aims: The non-vitamin K oral anticoagulant dabigatran etexilate (dabigatran) is increasingly prescribed to patients with non-valvular atrial fibrillation and venous thromboembolism. Adipose tissue (AT) inflammation during obesity plays a crucial role in the development of insulin resistance, type II diabetes and atherogenesis. The aim of the present study was to investigate the effects of thrombin inhibition by dabigatran in a combined model of diet-induced obesity and atherosclerosis., Methods: Female Low density lipoprotein receptor knockout (Lldr
-/- ) mice were fed a high-fat diet containing 5 mg/g dabigatran or matching control for 20 weeks., Results: Dabigatran-treated animals showed increased adipocyte hypertrophy, but reduced numbers of pro-inflammatory M1-polarized macrophages in the adipose tissue. Abundance of pro-inflammatory M1 macrophages was also decreased in the aortic wall of dabigatran-fed mice. Multiple circulating cytokines were reduced, indicating an effect in systemically relevant secretory compartments such as the AT., Conclusions: Dabigatran treatment reduces pro-inflammatory M1 macrophages in atherosclerotic lesions, thereby contributing to plaque stabilizing and atheroprotective effects of the thrombin inhibitor. This finding is not restricted to the vascular wall but is also present in AT where dabigatran treatment reduced the release of pro-inflammatory cytokines and accumulation of M1 macrophages., (Copyright © 2019 Elsevier B.V. All rights reserved.)- Published
- 2019
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