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Thromb Haemost 2017; 117(09): 1816-1827
DOI: 10.1160/TH17-03-069
Atherosclerosis and Ischaemic Disease
Schattauer GmbH

Molecular signature of coronary stent thrombosis: oxidative stress and innate immunity cells

Judit Cubedo   *
1   Cardiovascular Science Institute – ICCC, Biomedical Research Institute Sant Pau (IIB-Sant Pau) and CiberCV, Barcelona, Spain
,
Ana Blasco   *
2   Invasive Cardiology Department Puerta de Hierro Hospital, Majadahonda, Madrid, Spain
,
Teresa Padró
1   Cardiovascular Science Institute – ICCC, Biomedical Research Institute Sant Pau (IIB-Sant Pau) and CiberCV, Barcelona, Spain
,
Ilaria Ramaiola
1   Cardiovascular Science Institute – ICCC, Biomedical Research Institute Sant Pau (IIB-Sant Pau) and CiberCV, Barcelona, Spain
,
Oriol Juan-Babot
1   Cardiovascular Science Institute – ICCC, Biomedical Research Institute Sant Pau (IIB-Sant Pau) and CiberCV, Barcelona, Spain
,
Javier Goicolea
2   Invasive Cardiology Department Puerta de Hierro Hospital, Majadahonda, Madrid, Spain
,
José Antonio Fernández-Díaz
2   Invasive Cardiology Department Puerta de Hierro Hospital, Majadahonda, Madrid, Spain
,
Juan Francisco Oteo
2   Invasive Cardiology Department Puerta de Hierro Hospital, Majadahonda, Madrid, Spain
,
Lina Badimon
1   Cardiovascular Science Institute – ICCC, Biomedical Research Institute Sant Pau (IIB-Sant Pau) and CiberCV, Barcelona, Spain
3   Cardiovascular Research Chair UAB, Barcelona, Spain
› Institutsangaben Financial support: This work was supported by grants from the Spanish Ministry of Economy and Competitiveness of Science [SAF2016–76819–R to L. B.]; Institute of Health Carlos III, ISCIII [TERCEL RD16/00110018 and CB16/11/0041 to L. B.; and FIS PI16/01915 to T. P.]; FEDER ˵Una Manera de Hacer Europa”; and “CERCA Programme/Generalitat de Catalunya” Spain. We thank FIC-Fundacion Jesús Serra, Barcelona, Spain, for their continuous support.
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Publikationsverlauf

Received: 10. März 2017

Accepted after major revision: 13. Mai 2017

Publikationsdatum:
28. November 2017 (online)

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Summary

The clinical impact of in-stent thrombosis is high because it is associated with high mortality and 20 % of the patients suffer a recurrent event within the two following years. The aim of this study was to characterise the morphologic and proteomic profile of in-stent thrombi (IST) in comparison to thrombi developed on native coronary arteries (CT) to identify a differential molecular signature. The study included 45 patients with ST-elevation-myocardial-infarction (STEMI) treated by primary-percutaneous-intervention and thrombus aspiration: 21 had IST and 24 had CT. Thrombi were characterised by morphologic immunohistochemical analysis and differential proteomic profiling (2-DE+MALDI-TOF/TOF). Bioinformatic analysis revealed differences in proteins related to oxidative-stress and cell death/survival. IST showed a higher content of structural proteins (gelsolin, actin-cytoplasmic-1, tropomyosin, and myosin) together with an imbalance in redox-homeostasis related proteins (increased superoxide-dismutase and decreased peroxiredoxin-2 thrombus content), and a coordinated increase of chaperones (HSP60 and HSC70) and cellular quality control-related proteins (26S–protease-regulatory-subunit-7). These changes were reflected into a significant decrease in HSC70 systemic levels and a significant increase in advanced-oxidation-protein-products (AOPP) indicative of increased oxidative stress-mediated protein damage in IST. Our results reveal an imbalance in redox-related proteins indicative of an exacerbated oxidative-stress that leads to an accumulation of AOPP serum levels in IST. Moreover, the coordinated increase in chaperones and regulatory proteins reflects the activation of intracellular protection mechanisms to maintain protein integrity in IST. The failure to counterbalance the stress situation could trigger cellular apoptosis leading to the destabilization of the thrombus and to a worse prognosis of IST-STEMI-patients.

Supplementary Material to this article is available online at www.thrombosis-online.com.

Keywords

Acute myocardial infarction - thrombus - in-stent thrombosis - oxidative stress - chaperones

* Both authors contributed equally to this paper.


 

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