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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
1   Translational Research Laboratory, Catalan Institute of Oncology-IDIBELL, L’Hospitalet de Llobregat, Spain
2   Department of Cell Death and Proliferation, IIBB-CSIC-IDIBAPS, Barcelona, Spain
,
Xavier Muñoz
1   Translational Research Laboratory, Catalan Institute of Oncology-IDIBELL, L’Hospitalet de Llobregat, Spain
,
Pedro Recarte-Pelz
2   Department of Cell Death and Proliferation, IIBB-CSIC-IDIBAPS, Barcelona, Spain
,
Nadia Garcia
1   Translational Research Laboratory, Catalan Institute of Oncology-IDIBELL, L’Hospitalet de Llobregat, Spain
,
Anna Luque
3   Cardiovascular Research Center, ICCC, Barcelona, Spain
,
Jerzy Krupinski
3   Cardiovascular Research Center, ICCC, Barcelona, Spain
4   Department of Neurology, Stroke Unit, Hospital Universitari Mutua de Terrassa, Terrassa, Spain
5   Fundacio IDIBELL, Barcelona, Spain
6   School of Biology, Chemistry and Health Science, and Faculty of Medical and Human Sciences, University of Manchester, Manchester, UK
,
Núria Sala
1   Translational Research Laboratory, Catalan Institute of Oncology-IDIBELL, L’Hospitalet de Llobregat, Spain
,
Pablo García de Frutos
2   Department of Cell Death and Proliferation, IIBB-CSIC-IDIBAPS, Barcelona, Spain
› Institutsangaben Financial support: We acknowledge grants SAF2006–07681 and BFU2007–61699/BFI from the Spanish Ministry of Science and Innovation; Marató de TV3 2008–121 from Fundació la Marató de TV3, PI081420 from the ISCIII, Spanish Ministry of Health. XM, NG and NS are members of the ISCIII network RTICCC (ISCIII DR06/0020). XM was supported by ISCIII CA06/0200 and BH has been recipient (2004–2008) of a grant from the Institut d’Investigació Biomèdica de Bellvitge (IDIBELL06/IDB-001).
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Publikationsverlauf

Received: 01. Oktober 2010

Accepted after major revision: 25. Januar 2011

Publikationsdatum:
28. November 2017 (online)

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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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