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Decreased M1 macrophage polarization in dabigatran-treated Ldlr-deficient mice: Implications for atherosclerosis and

Kathrin Feldmann1, Maria Grandoch1, Christina Kohlmorgen1

  • 1Institute for Pharmacology and Clinical Pharmacology, Medical Faculty, University Hospital, Heinrich-Heine-University Duesseldorf, Duesseldorf, Germany; Cardiovascular Research Institute Duesseldorf (CARID), University Hospital, Heinrich-Heine-University Duesseldorf, Duesseldorf, Germany.

Atherosclerosis
|June 25, 2019
PubMed

Insights

Dabigatran, an oral anticoagulant, reduces pro-inflammatory M1 macrophages in adipose tissue and atherosclerotic lesions. This thrombin inhibitor demonstrates atheroprotective effects by stabilizing plaques and reducing systemic inflammation.

Area of Science:

  • Cardiovascular Pharmacology
  • Metabolic Disease Research
  • Immunology

Background:

  • Obesity-induced adipose tissue inflammation contributes to insulin resistance, type II diabetes, and atherosclerosis.
  • Non-vitamin K oral anticoagulants like dabigatran etexilate are increasingly used for atrial fibrillation and venous thromboembolism.

Purpose of the Study:

  • To investigate the impact of thrombin inhibition by dabigatran on diet-induced obesity and atherosclerosis.
  • To evaluate dabigatran's effects on adipose tissue inflammation and macrophage polarization in a combined disease model.

Main Methods:

  • Female Low density lipoprotein receptor knockout (Ldlr-/-) mice were fed a high-fat diet supplemented with dabigatran or a control for 20 weeks.
  • Analysis of adipose tissue and aortic wall for macrophage populations (M1 polarization) and adipocyte characteristics.

Main Results:

  • Dabigatran treatment led to increased adipocyte hypertrophy but decreased pro-inflammatory M1 macrophages in adipose tissue.
  • Reduced M1 macrophage abundance was observed in the aortic wall of dabigatran-fed mice.
  • Circulating levels of multiple pro-inflammatory cytokines were decreased, suggesting systemic effects.

Conclusions:

  • Dabigatran treatment reduces pro-inflammatory M1 macrophages in atherosclerotic lesions, promoting plaque stabilization and atheroprotection.
  • These beneficial effects extend to adipose tissue, where dabigatran decreases pro-inflammatory cytokine release and M1 macrophage accumulation.
Abstract

Keywords:
AtherosclerosisInflammationMacrophageObesityThrombin inhibitor

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