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

Judit Cubedo; Ana Blasco; Teresa Padró; Ilaria Ramaiola; Oriol Juan-Babot; Javier Goicolea; José Antonio Fernández-Díaz; Juan Francisco Oteo; Lina Badimon

doi:10.1160/TH17-03-069

Thrombosis and Haemostasis, Table of Contents

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

Authors

Judit Cubedo^*

¹Cardiovascular Science Institute – ICCC, Biomedical Research Institute Sant Pau (IIB-Sant Pau) and CiberCV, Barcelona, Spain
Ana Blasco^*

²Invasive Cardiology Department Puerta de Hierro Hospital, Majadahonda, Madrid, Spain
Teresa Padró

¹Cardiovascular Science Institute – ICCC, Biomedical Research Institute Sant Pau (IIB-Sant Pau) and CiberCV, Barcelona, Spain
Ilaria Ramaiola

¹Cardiovascular Science Institute – ICCC, Biomedical Research Institute Sant Pau (IIB-Sant Pau) and CiberCV, Barcelona, Spain
Oriol Juan-Babot

¹Cardiovascular Science Institute – ICCC, Biomedical Research Institute Sant Pau (IIB-Sant Pau) and CiberCV, Barcelona, Spain
Javier Goicolea

²Invasive Cardiology Department Puerta de Hierro Hospital, Majadahonda, Madrid, Spain
José Antonio Fernández-Díaz

²Invasive Cardiology Department Puerta de Hierro Hospital, Majadahonda, Madrid, Spain
Juan Francisco Oteo

²Invasive Cardiology Department Puerta de Hierro Hospital, Majadahonda, Madrid, Spain
Lina Badimon

¹Cardiovascular Science Institute – ICCC, Biomedical Research Institute Sant Pau (IIB-Sant Pau) and CiberCV, Barcelona, Spain

³Cardiovascular Research Chair UAB, Barcelona, Spain

Abstract

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

Full Text

References

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Supplementary Material

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