Aspirin influences megakaryocytic gene expression leading to up-regulation of multidrug resistance protein-4 in human platelets.
Bottom Line: We recently found that platelet MRP4 overexpression has a role in reducing aspirin action in patients after by-pass surgery.In DAMI cells, aspirin and WY14643 treatment induced a significant increase in MRP4 and PPARα expression.This work represents an innovative and attractive approach, useful both to identify patients less sensitive to aspirin and to improve pharmacological treatment in cardiovascular high-risk patients.
Affiliation: Department of Experimental Medicine, Sapienza University of Rome, Rome.Show MeSH
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Mentions: To confirm further the involvement of PPARα in MRP4 up-regulation, DAMI cells were transfected with PPARα specific siRNA (PPAR-si). Cells transfected with PPAR-si did not show any significant increase of PPARα mRNA and protein expression after aspirin and WY14643 treatment while cells transfected with control non-specific siRNA (CTR-si) showed the same aspirin and WY14643 induced expression changes observed in untrasfected cells (Figure 4A and B). Similarly, no increase of aspirin and WY14643 dependent MRP4 expression was detected in cells treated with PPAR-si, unlike those found in CTR-si transfected cells (Figure 4C).
Affiliation: Department of Experimental Medicine, Sapienza University of Rome, Rome.