Highlights
- What is the current knowledge on the topic?
- Aspirin is widely prescribed to prevent cardiovascular disease
through inhibition of platelet COX-1. Aspirin is known to have
effects beyond inhibiting platelet COX-1; however, characterization
of non-COX1 effects in platelets has been lacking.
- What question did this study address?
- This study comprehensively characterized the on- and off-target
effects of aspirin on platelet gene expression and platelet
function.
- What does this study add to our knowledge?
- Using an experimental protocol of human aspirin exposure and serial
platelet transcriptomic and functional testing, we identified a
non-canonical effect of aspirin on inhibiting protein synthesis
pathways in platelets. This effect acts to attenuate the platelet
inhibitory effects of aspirin on platelet COX-1
- How might this change clinical pharmacology or translational science?
- Compared to low-dose aspirin we found no major differences with
high-dose aspirin with respect to platelet function or platelet
transcriptome and thus no rationale for using high-dose aspirin.
Patients chronically prescribed aspirin to prevent cardiovascular
disease that have an accentuated platelet transcriptional response
may experience smaller than expected reductions in cardiovascular
risk.