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Updated: May 1, 2026
Quantification of Atherosclerosis in Mice
Published on: June 12, 2019
Thrombin inhibition by dabigatran attenuates atherosclerosis in ApoE deficient mice
Simon Pingel1, Vedat Tiyerili1, Jens Mueller2
1Medizinische Klinik und Poliklinik II, Universitätsklinikum, Bonn, Germany.
Insights
The thrombin inhibitor dabigatran effectively reduced atherosclerosis in mice by lowering oxidative stress and inflammation. This study highlights dabigatran
Area of Science:
- Cardiovascular Research
- Pharmacology
- Inflammation Biology
Background:
- Atherosclerosis is a chronic inflammatory disease involving endothelial damage, immune cell infiltration, and procoagulation.
- The interaction between thrombin and atherogenesis is recognized, but specific therapeutic targets remain elusive.
Purpose of the Study:
- To investigate the therapeutic potential of the direct thrombin inhibitor dabigatran in a mouse model of atherosclerosis.
- To assess the effects of dabigatran on vascular oxidative stress, endothelial function, and atherosclerotic lesion development.
Main Methods:
- Atherosclerosis-prone ApoE(-/-) mice were fed a cholesterol-rich diet and treated with either placebo or dabigatran.
- Vascular oxidative stress was measured using L012 chemiluminescence.
- Endothelial function was assessed via organ chamber experiments on isolated aortic rings.
- Atherosclerotic lesion size and macrophage infiltration were quantified through histological and immunohistological analyses.
Main Results:
- Dabigatran treatment significantly prolonged thrombin time, confirming its inhibitory effect.
- Vascular oxidative stress was markedly reduced in dabigatran-treated mice.
- Endothelium-dependent vasorelaxation was significantly improved by dabigatran.
- Dabigatran significantly decreased atherosclerotic lesion area and macrophage infiltration in the aortic root.
- No significant changes in blood pressure, body weight, or food intake were observed.
Conclusions:
- The direct thrombin inhibitor dabigatran demonstrates significant anti-atherosclerotic effects in mice.
- Dabigatran reduces vascular oxidative stress and inflammation, key contributors to atherosclerosis.
- Improved endothelial function and decreased atherosclerotic burden underscore dabigatran's therapeutic potential in cardiovascular disease.
Introduction:
Atherosclerosis is a chronic inflammatory disease characterized by endothelial cell damage, infiltration, proliferation and accumulation of macrophages, lymphocytes and transformed vascular smooth muscle cells within the vascular wall and procoagulation processes involving activation of plasmatic coagulation events and platelets. Numerous studies suggested a close interaction between thrombin action and atherogenesis, but possibly underlying mechanisms are multiple and specific treatment options were missing until now.
Material And Methods:
Atherosclerosis prone 12 weeks old ApoE(-/-) mice were fed a cholesterol rich diet for 4 weeks and were concomitantly treated orally with placebo or the thrombin inhibitor dabigatran (1.2 g/kg/day).
Results:
The thrombin time (HEMOCLOT(®)) was significant extended in dabigatran treated animals. Vascular oxidative stress was significantly reduced during thrombin inhibition, as assessed by L012 chemiluminescence in aortic segments (212 ±84 vs. 69 ±21 RLU/s/mg dry weight, p = 0.048). Organ chamber experiments of isolated aortic rings showed that dabigatran treatment significantly improved endothelium-derived vasorelaxation (p < 0.001). Dabigatran treated mice developed less atherosclerotic lesions (6.2 ±0.2% vs. 9 ±1.1%, p = 0.037) and showed less infiltration of atherosclerotic lesions with macrophages (2.59 ±0.3% vs. 5.14 ±0.7%, p = 0.0046), as determined by systematic histological and immunohistological analyses of the aortic root. Blood pressure, body weight and food intake were not altered by the treatment.
Conclusions:
The thrombin inhibitor dabigatran reduces vascular oxidative stress and inflammation, improves endothelial function and decreases atherosclerosis in mice.
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