Role of thrombin in the pathogenesis of atherosclerosis

J Cell Biochem. 2019 Apr;120(4):4757-4765. doi: 10.1002/jcb.27771. Epub 2018 Sep 30.

Abstract

Atherosclerosis is an arterial disease associated with inflammation. Thrombin is a procoagulant and proinflammatory serine protease that contributes to the pathology of atherosclerosis by enhancing the expression of cell adhesion molecules, inducing the secretion of proinflammatory cytokines, activating inflammatory responses in atherosclerotic plaques, stimulating proliferation of aortic smooth muscle cells, and exacerbating vascular lesions at sites of injury. Hence, thrombin appears to be an important target for treatment of atherosclerosis and thrombin pharmacological inhibitors have significant therapeutic potency for suppressing inflammatory responses in cardiovascular diseases. This review summarizes the proinflammatory signaling functions of thrombin as well as the therapeutic potency of thrombin inhibitors in the pathogenesis of atherosclerosis and hence their potential therapeutic value in this condition.

Keywords: atherosclerosis; inflammation; thrombin; thrombin inhibitors.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Aorta / metabolism
  • Aorta / pathology*
  • Atherosclerosis / drug therapy
  • Atherosclerosis / metabolism*
  • Atherosclerosis / pathology
  • Humans
  • Inflammation / drug therapy
  • Inflammation / metabolism
  • Inflammation / pathology
  • Muscle, Smooth, Vascular / metabolism*
  • Muscle, Smooth, Vascular / pathology
  • Myocytes, Smooth Muscle / metabolism*
  • Myocytes, Smooth Muscle / pathology
  • Plaque, Atherosclerotic / drug therapy
  • Plaque, Atherosclerotic / metabolism*
  • Plaque, Atherosclerotic / pathology
  • Signal Transduction
  • Thrombin / antagonists & inhibitors
  • Thrombin / metabolism*

Substances

  • Thrombin