Increased secretion of Gas6 by smooth muscle cells in human atherosclerotic carotid plaques

Sylvain Clauser; Olivier Meilhac; Ivan Bièche; Pierre Raynal; Patrick Bruneval; Jean-Baptiste Michel; Delphine Borgel

doi:10.1160/TH11-05-0368

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2012; 107(01): 140-149
DOI: 10.1160/TH11-05-0368

Cardiovascular Biology and Cell Signalling

Schattauer GmbH

Increased secretion of Gas6 by smooth muscle cells in human atherosclerotic carotid plaques

Authors

Sylvain Clauser

¹EA 4531, Université Paris-Sud, Châtenay-Malabry, France

²AP-HP, Hôpital Ambroise Paré, Boulogne-Billancourt, France

³Faculté de Médecine, Université de Versailles-Saint Quentin, Guyancourt, France
Olivier Meilhac

⁴INSERM U698, Paris, France

⁵AP-HP, CHU X-Bichat, Paris, France

⁶Université Paris Diderot, Paris, France
Ivan Bièche

⁷INSERM UMR S745, Faculté de Pharmacie, Paris, France

⁸Université Paris Descartes, Paris, France
Pierre Raynal

⁹Centre Hospitalier de Versailles, Le Chesnay, France
Patrick Bruneval

⁸Université Paris Descartes, Paris, France

¹⁰INSERM U970, Paris, France

¹¹AP-HP, Hôpital Européen Georges-Pompidou, Paris, France
Jean-Baptiste Michel

⁴INSERM U698, Paris, France

⁵AP-HP, CHU X-Bichat, Paris, France

⁶Université Paris Diderot, Paris, France
Delphine Borgel

¹EA 4531, Université Paris-Sud, Châtenay-Malabry, France

²AP-HP, Hôpital Ambroise Paré, Boulogne-Billancourt, France

Abstract

Summary

Vitamin K-dependent protein Gas6 (growth-arrest specific gene 6) plays a role in vascular smooth muscle cell (VSMC) survival and migration, as well as in endothelium and leukocyte activation, and could therefore be involved in atherosclerosis. However, the study of mouse models has led to contradictory results regarding the pro- or anti-atherogenic properties of Gas6, and relatively few data are available in human pathophysiology. To better understand the implication of Gas6 in human atherosclerosis, we studied Gas6 expression and secretion in vitro in human VSMC, and analysed the effect of Gas6 on inflammatory gene expression in these cells. We show that Gas6 secretion in VSMC is strongly induced by the anti-inflammatory cytokine transforming growth factor (TGF)β, and that VSMC stimulation by recombinant Gas6 decreases the expression of inflammatory genes tumour necrosis factor (TNF)α and intracellular adhesion molecule (ICAM)-1. The study of Gas6 expression in human carotid endarterectomy samples revealed that Gas6 is mainly expressed by VSMC at all stages of human atherosclerosis, but is not detected in normal vessel wall. Analysis of plaque secretomes showed that Gas6 secretion is markedly higher in non-complicated plaques than in complicated plaques, and that TGFβ secretion pattern mirrors that of Gas6. We conclude that Gas6 is secreted in human atherosclerotic plaques by VSMC following stimulation by TGFβ, and that Gas6 secretion decreases with plaque complication. Therefore, we propose that Gas6 acts as a protective factor, in part by reducing the pro-inflammatory phenotype of VSMC.

Keywords

Atherosclerosis - Gas6 - vascular smooth muscle cells - TGFβ

Full Text

References

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