Expression of the vitamin K-dependent proteins GAS6 and protein S and the TAM receptor tyrosine kinases in human atherosclerotic carotid plaques

Begoña Hurtado; Xavier Muñoz; Pedro Recarte-Pelz; Nadia Garcia; Anna Luque; Jerzy Krupinski; Núria Sala; Pablo García de Frutos

doi:10.1160/TH10-10-0630

Thrombosis and Haemostasis, Inhaltsverzeichnis

Thromb Haemost 2011; 105(05): 873-882
DOI: 10.1160/TH10-10-0630

Cardiovascular Biology and Cell Signalling

Schattauer GmbH

Expression of the vitamin K-dependent proteins GAS6 and protein S and the TAM receptor tyrosine kinases in human atherosclerotic carotid plaques

Begoña Hurtado

¹Translational Research Laboratory, Catalan Institute of Oncology-IDIBELL, L’Hospitalet de Llobregat, Spain

²Department of Cell Death and Proliferation, IIBB-CSIC-IDIBAPS, Barcelona, Spain

,

Xavier Muñoz

¹Translational Research Laboratory, Catalan Institute of Oncology-IDIBELL, L’Hospitalet de Llobregat, Spain

,

Pedro Recarte-Pelz

²Department of Cell Death and Proliferation, IIBB-CSIC-IDIBAPS, Barcelona, Spain

,

Nadia Garcia

¹Translational Research Laboratory, Catalan Institute of Oncology-IDIBELL, L’Hospitalet de Llobregat, Spain

,

Anna Luque

³Cardiovascular Research Center, ICCC, Barcelona, Spain

,

Jerzy Krupinski

³Cardiovascular Research Center, ICCC, Barcelona, Spain

⁴Department of Neurology, Stroke Unit, Hospital Universitari Mutua de Terrassa, Terrassa, Spain

⁵Fundacio IDIBELL, Barcelona, Spain

⁶School of Biology, Chemistry and Health Science, and Faculty of Medical and Human Sciences, University of Manchester, Manchester, UK

,

Núria Sala

¹Translational Research Laboratory, Catalan Institute of Oncology-IDIBELL, L’Hospitalet de Llobregat, Spain

,

Pablo García de Frutos

²Department of Cell Death and Proliferation, IIBB-CSIC-IDIBAPS, Barcelona, Spain

› Institutsangaben

Abstract

Summary

The GAS6/ProS-TAM system is composed of two vitamin K-dependent ligands (GAS6 and protein S) and their three protein tyrosine kinase receptors TYRO3, AXL and MERTK, known as the TAM receptors. The system plays a prominent role in conditions of injury, inflammation and repair. In murine models of atherosclerotic plaque formation, mutations in its components affect atherosclerosis severity. Here we used Taqman low-density arrays and immunoblotting to study mRNA and protein expression of GAS6, ProS and the TAM receptors in human carotid arteries with different degrees of atherosclerosis. The results show a clear down-regulation of the expression of AXL in atheroma plaques with respect to normal carotids that is matched by decreased abundance of AXL in protein extracts detected by immunoblotting. A similar decrease was observed in PROS1 mRNA expression in atherosclerotic carotids compared to the normal ones, but in this case protein S (ProS) was clearly increased in protein extracts of carotid arteries with increasing grade of atherosclerosis, suggesting that ProS is carried into the plaque. MERTK was also increased in atherosclerotic carotid arteries with respect to the normal ones, suggesting that the ProS-MERTK axis is functional in advanced human atherosclerotic plaques. MERTK was expressed in macrophages, frequently in association with ProS, while ProS was abundant also in the necrotic core. Our data suggest that the ProS-MERTK ligand-receptor pair was active in advanced stages of atherosclerosis, while AXL signalling is probably down-regulated.

Keywords

PROS1 - GAS6 - TYRO3 - AXL - MERTK, - arterioesclerosis - atheroma - carotid plaque - vitamin K-dependent proteins - receptor tyrosine kinases

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Referenzen

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