Pleiotropic role of growth arrest-specific gene 6 in atherosclerosis.
OBJECTIVE
Growth arrest-specific gene 6 (Gas6) belongs to the family of vitamin K-dependent coagulation proteins, but in contrast to its other members, has only a limited role in hemostasis. Instead, Gas6 plays a prominent role in conditions of injury, inflammation and repair. Gas6 amplifies the activation of various cell types including endothelial cells and platelets in different models of thrombosis and inflammation, processes also important in atherosclerosis.


RESULTS
Recently, we showed that in human and murine atherosclerotic plaques, Gas6 is expressed by endothelial cells, smooth muscle cells and most abundantly by macrophages, and that its expression increases with atherosclerosis severity. Moreover, genetic loss of Gas6 in ApoE mice reduced the influx of inflammatory cells in the plaque and induced plaque fibrosis, hence creating a stable plaque phenotype. Consistent herewith, Gas6 plasma levels are increased in patients with unstable angina pectoris, which is a common consequence of atherosclerotic plaque rupture.


CONCLUSIONS
Inhibition of Gas6 would be an attractive therapeutic target for stabilizing atherosclerotic plaques and for the prevention of vascular thrombotic occlusion after plaque rupture. Here we will critically review the existing literature on the potential roles of Gas6 and its receptors in the different stages of atherosclerosis.
Tjwa
Marc
M
Leibniz AG Vascular Hematology, Center for Molecular Medicine, Institute of Cardiovascular Regeneration, University of Frankfurt, Germany.
Moons
Lieve
L
Lutgens
Esther
E
D000818:Animals; D050197:Atherosclerosis / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D042783:Endothelial Cells / Q000378:metabolism; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D007962:Leukocytes / Q000276:immunology / Q000378:metabolism; D009336:Necrosis / Q000378:metabolism; D000099255:Growth Arrest-Specific Protein 6
D036341:Intercellular Signaling Peptides and Proteins; D000099255:Growth Arrest-Specific Protein 6