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. 2016 Mar 15:14:74.
doi: 10.1186/s12967-016-0827-7.

The lack of aspirin resistance in patients with coronary artery disease

Nóra Homoródi  1 , Emese G Kovács  1   2 , Sarolta Leé  3 , Éva Katona  2 , Amir H Shemirani  4 , Gizella Haramura  2 , László Balogh  1 , Zsuzsanna Bereczky  2 , Gabriella Szőke  5 , Hajna Péterfy  5 , Róbert G Kiss  3 , István Édes  1 , László Muszbek  6   7
Affiliations

The lack of aspirin resistance in patients with coronary artery disease

Nóra Homoródi et al. J Transl Med. .

Abstract

Background: Aspirin resistance established by different laboratory methods is still a debated problem. Using COX1 specific methods no aspirin resistance was detected among healthy volunteers. Here we tested the effect of chronic aspirin treatment on platelets from patients with stable coronary artery disease. The expression of COX2 mRNA in platelets and its influences on the effect of aspirin was also investigated.

Methods: One hundred and forty four patients were enrolled in the study. The direct measurement of COX1 acetylation was carried out by monoclonal antibodies specific to acetylated and non-acetylated COX1 (acCOX1 and nacCOX1) using Western blotting technique. Arachidonic acid (AA) induced TXB2 production by platelets was measured by competitive immunoassay. AA induced platelet aggregation, ATP secretion and VerifyNow Aspirin Assay were also performed. COX2 and COX1 mRNA expression in platelets were measured in 56 patients by RT-qPCR.

Results: In 138 patients only acCOX1 was detected, in the remaining six patients nacCOX1 disappeared after a compliance period. AA induced TXB2 production by platelets was very low in all patients including the 6 patients after compliance. AA induced platelet aggregation, secretion and with a few exceptions the VerifyNow Assay also demonstrated the effect of aspirin. Smoking, diabetes mellitus and inflammatory conditions did not influence the results. The very low amount of COX2 mRNA detected in 39 % of the investigated platelets did not influence the effect of aspirin.

Conclusions: No aspirin resistance was detected among patients with stable coronary artery disease. COX2 expression in platelets did not influence the effect of aspirin.

Keywords: Aspirin; Coronary artery disease; Cyclooxygenase-1; Cyclooxygenase-2; Platelet; Thromboxane B2.

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Figures

Fig. 1
Fig. 1
Detection of acetylated COX1 (acCOX1, lower panel) and non-acetylated COX1 (nacCOX1, upper panel) in platelet lysate of non-treated controls (C) and patients on aspirin treatment (P1–P4). Monoclonal antibodies specific to the acetylated and non-acetylated forms of COX1 were used in Western blotting detection system. In patients P3 and P4 non-compliance was presumed and the test was repeated after a 2 weeks period of compliance (P3/2 and P4/2). Below the band representing COX-1 another low intensity band cross-reacting with both antibodies is also apparent. It very likely represents COX-1 isoform 2, a 37 amino acids shorter transcript variant (http://www.ncbi.nlm.nih.gov/nuccore/18104968)
Fig. 2
Fig. 2
Arachidonic acid induced TXB2 generation of platelets from controls (open square) and from patients with coronary artery disease being on long-term aspirin treatment (filled circle). IQR interquartile range
Fig. 3
Fig. 3
The results of arachidonic acid induced platelet aggregation and VerifyNow Aspirin Assay in controls (open square) and in patients with coronary artery disease being on long-term aspirin treatment (filled circle). IQR interquartile range
Fig. 4
Fig. 4
COX2:COX1 mRNA ratios in the platelets of patients with detectable COX2 mRNA
See this image and copyright information in PMC

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