The hemostatic system as a regulator of inflammation in atherosclerosis

IUBMB Life. 2014 Nov;66(11):735-44. doi: 10.1002/iub.1333. Epub 2014 Dec 9.

Abstract

Atherosclerosis is a chronic inflammatory disease of the arterial vessel wall. As part of a tightly connected cross-talk between inflammation and coagulation, there is growing evidence that the coagulation system plays a pivotal role in the development and progression of atherosclerosis. We here discuss the presence of coagulation factors in atherosclerotic lesions and the overall effects of hypercoagulability and hypocoagulability on atherosclerotic lesion formation. Moreover, we focus on the unifying common pathway of coagulation, which can be initiated by the intrinsic and extrinsic pathway of coagulation, and discuss the functions of the coagulation factors FX, thrombin, and FXIII as regulators of inflammation in atherosclerosis. In particular, we review the non-hemostatic and immune-modulatory functions of these factors in endothelial and smooth muscle cells, as well as monocytes/macrophages, but also other cells, such as dendritic cells and T cells, that may control the inflammatory process of atherosclerosis. Their multiple roles in coagulation, but also their non-hemostatic functions in different cell types in inflammation and immunity, may harbor great potential for the development of novel therapeutic approaches for treating cardiovascular disease.

Keywords: FX; FXIII; atherosclerosis; coagulation; hemostasis; immunity; inflammation; thrombin.

Publication types

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

MeSH terms

  • Animals
  • Atherosclerosis / drug therapy
  • Atherosclerosis / physiopathology*
  • Blood Coagulation / physiology*
  • Blood Coagulation Factors / metabolism*
  • Carbohydrate Epimerases / metabolism
  • Cell Line / drug effects
  • Disease Models, Animal
  • Factor XIII / metabolism
  • Genetic Pleiotropy / physiology*
  • Humans
  • Inflammation / physiopathology*
  • Ketone Oxidoreductases / metabolism
  • Mice
  • Myocytes, Smooth Muscle / metabolism*
  • Thrombin / metabolism

Substances

  • Blood Coagulation Factors
  • Factor XIII
  • TSTA3 protein, human
  • Ketone Oxidoreductases
  • Thrombin
  • Carbohydrate Epimerases