Different expression of proteins in platelets from aspirin-resistant and aspirin-sensitive patients.
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 + or - 220.6 vs. 4273.3 + or - 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 + or - 3.8 vs. 48.8 + or - 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.
Mateos-Cáceres
Petra J
PJ
Cardiovascular Research Unit, Cardiology Department and Cardiovascular Institute, Hospital Clínico San Carlos, Madrid, Spain.
Macaya
Carlos
C
Azcona
Luis
L
Modrego
Javier
J
Mahillo
Estela
E
Bernardo
Esther
E
Fernandez-Ortiz
Antonio
A
López-Farré
Antonio J
AJ
D000368:Aged; D001241:Aspirin / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D001798:Blood Proteins / Q000032:analysis*; D015153:Blotting, Western; D002470:Cell Survival; D003598:Cytoskeletal Proteins / Q000097:blood; D004351:Drug Resistance; D015180:Electrophoresis, Gel, Two-Dimensional; D004734:Energy Metabolism; D005260:Female; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood; D008297:Male; D013058:Mass Spectrometry; D008875:Middle Aged; D017202:Myocardial Ischemia / Q000097:blood / Q000188:drug therapy*; D018384:Oxidative Stress; D010449:Peptide Mapping; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D010979:Platelet Function Tests; D040901:Proteomics / Q000379:methods; D016896:Treatment Outcome
D015415:Biomarkers; D001798:Blood Proteins; D003598:Cytoskeletal Proteins; D018836:Inflammation Mediators; D010975:Platelet Aggregation Inhibitors; D001241:Aspirin