Platelet Carbonic Anhydrase II, a Forgotten Enzyme, May Be Responsible for Aspirin Resistance

Abstract

Background Thromboembolic events constitute a major health problem, despite the steadily expanding arsenal of antiplatelet drugs. Hence, there is still a need to optimize the antiplatelet therapy. Objectives The aim of our study was to verify a hypothesis that there are no differences in platelet proteome between two groups of healthy people representing different acetylsalicylic acid (aspirin) responses as assessed by the liquid chromatography/mass spectrometry (LC/MS) technique. Patients/Methods A total of 61 healthy volunteers were recruited for the study. Physical examination and blood collection were followed by platelet-rich plasma aggregation assays and platelet separation for proteomic LC/MS analysis. Arachidonic acid- (AA-) induced aggregation (in the presence of aspirin) allowed to divide study participants into two groups aspirin-resistant (AR) and aspirin-sensitive (AS) ones. Subsequently, platelet proteome was compared in groups using the LC/MS analysis. Results The LC/MS analysis of platelet proteome between groups revealed that out of all identified proteins, the only discriminatory protein, affecting aspirin responsiveness, is platelet carbonic anhydrase II (CA II). Conclusions CA II is a platelet function modulator and should be taken into consideration as a cardiovascular event risk factor or therapeutic target.

Molecular Proteomics and Signalling of Human Platelets in Health and Disease

“…Using a label-free proteomic approach, platelets obtained from cord blood, which relatively poorly respond to thromboxane stimulation, express normal receptor levels, but are enriched in mitochondrial energy and metabolism proteins, including NDUFS1, NDUFA10, NDUFAS and NDUFY2 [94]. A perhaps accidental finding due to low sample size was that platelets from good and poor responders to aspirin treatment were differentiated in the level of carbonic anhydrase II [95].…”

The Human Carbonic Anhydrase II in Platelets: An Underestimated Field of Its Activity

“…Nevertheless, in a recent report we provided evidence that interindividual variability in in vitro platelet responsiveness to acetylsalicylic acid may be associated with carbonic anhydrase II concentration. Briefly, ASA low-responders presented increased intraplatelet CAII concentration and more intense baseline arachidonic acid induces aggregation compared to ASA sensitive individuals [ 123 ]. Among the CAII-dependent mechanisms modifying the platelet responsiveness, the pH changes of platelet cytosol leading to impaired acetylating of cyclooxygenase by ASA are noteworthy.…”

Aspirin: A Suicide Inhibitor of Carbonic Anhydrase II

“…The short half-life of Aspirin leads to patients taking the drug daily to keep a therapeutic dose in their system. A recent study found in a genome-wide search that CAII is the only protein overexpressed in patients with Aspirin resistance and therefore may be the unidentified carboxylesterase [24]. Since Aspirin is a carboxylic acid-based molecule, it was hypothesized that it could potentially bind to CAII.…”