Different expression of proteins in platelets from aspirin-resistant and aspirin-sensitive patients

Petra J. Mateos-Cáceres; Carlos Macaya; Luis Azcona; Javier Modrego; Estela Mahillo; Esther Bernardo; Antonio Fernández-Ortiz; Antonio J. López-Farré

doi:10.1160/TH09-05-0290

Thrombosis and Haemostasis, Inhaltsverzeichnis

Thromb Haemost 2010; 103(01): 160-170
DOI: 10.1160/TH09-05-0290

Platelets and Blood Cells

Schattauer GmbH

Different expression of proteins in platelets from aspirin-resistant and aspirin-sensitive patients

Petra J. Mateos-Cáceres

¹Cardiovascular Research Unit, Cardiology Department and Cardiovascular Institute, Hospital Clínico San Carlos, Madrid, Spain

,

Carlos Macaya

¹Cardiovascular Research Unit, Cardiology Department and Cardiovascular Institute, Hospital Clínico San Carlos, Madrid, Spain

²Coronary Unit, Cardiology Department and Cardiovascular Institute, Hospital Clínico San Carlos, Madrid, Spain

,

Luis Azcona

¹Cardiovascular Research Unit, Cardiology Department and Cardiovascular Institute, Hospital Clínico San Carlos, Madrid, Spain

,

Javier Modrego

¹Cardiovascular Research Unit, Cardiology Department and Cardiovascular Institute, Hospital Clínico San Carlos, Madrid, Spain

,

Estela Mahillo

¹Cardiovascular Research Unit, Cardiology Department and Cardiovascular Institute, Hospital Clínico San Carlos, Madrid, Spain

,

Esther Bernardo

²Coronary Unit, Cardiology Department and Cardiovascular Institute, Hospital Clínico San Carlos, Madrid, Spain

,

Antonio Fernández-Ortiz

²Coronary Unit, Cardiology Department and Cardiovascular Institute, Hospital Clínico San Carlos, Madrid, Spain

,

Antonio J. López-Farré

¹Cardiovascular Research Unit, Cardiology Department and Cardiovascular Institute, Hospital Clínico San Carlos, Madrid, Spain

› Institutsangaben

Abstract

Summary

The aim of the present study was to analyse differences in the protein expression profile between platelets from aspirin (ASA)-resistant patients and ASA-sensitive patients. We analysed platelets from 51 clinically stable coronary ischaemic patients taking ASA (100 mg/day) divided into ASA-resistant (n=25) and ASA-sensitive (n=26) based on a platelet functionality test (PFA-100). Proteins associated with cytoskeleton, energetic metabolism, oxidative stress, inflammation and cell survival were analysed by two-dimensional electrophoresis and mass spectrometry. The expression of two gelsolin precursor isotypes and one F-acting capping protein isotype was decreased in ASA-resistant platelets (p<0.05). The expression of glyceraldehyde 3-phosphate dehydrogenase was increased in the ASA-resistant platelets (1751.1 ± 220.6 vs. 4273.3 ± 971.7, 95% confidence interval [CI] 1815.11 to 4061.2, p=0.001). It was accompanied by a reduced expression and activity of 1,6-bisphosphate aldolase in platelets without changes in the content of pyruvate. A reduced expression of gluthathione-S-transferase and the protein disulfide isomerase isotype 1 was found in ASA-resistant platelets. The protein expression of the chloride intracellular channel isotype 1 was increased in ASA-resistant platelets (21.3 ± 3.8 vs. 48.8 ± 6.0, CI 29.5 to 45.95, p=0.03) while the expression of two HSP60 and two HSP71 isotypes was decreased. No changes were observed in proteins associated with inflammation. In conclusion, ASA-resistant and ASA-sensitive platelets are different in terms of the level of expression of proteins associated with mechanisms such as energetic metabolism, cytoskeleton, oxidative stress and cell survival which may be associated with their different ability to respond to ASA.

Keywords

Platelet - aspirin resistance - coronary ischaemia - proteins

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Referenzen

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