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Aspirin influences megakaryocytic gene expression leading to up-regulation of multidrug resistance protein-4 in human platelets.

Massimi I, Guerriero R, Lotti LV, Lulli V, Borgognone A, Romani F, Barillà F, Gaudio C, Gabbianelli M, Frati L, Pulcinelli FM - Br J Clin Pharmacol (2014)

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.

View Article: PubMed Central - PubMed

Affiliation: Department of Experimental Medicine, Sapienza University of Rome, Rome.

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Related in: MedlinePlus

MRP4 expression after aspirin suspension in DAMI cells. Q-RT-PCR analysis of endogenous MRP4 and PPARα expression in DAMI cells, in either untreated (Ctr) or treated, for 48 h, with 50 μm aspirin (ASA) or after 2, 5 and 7 days of aspirin suspension (wash out, WO). Data were normalized with the mean of the fold induction of GAPDH, ACTB and CD42B expression and reported as mean ± SD of three experiments (NS = not significant, *P < 0.05; t-test)
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fig03: MRP4 expression after aspirin suspension in DAMI cells. Q-RT-PCR analysis of endogenous MRP4 and PPARα expression in DAMI cells, in either untreated (Ctr) or treated, for 48 h, with 50 μm aspirin (ASA) or after 2, 5 and 7 days of aspirin suspension (wash out, WO). Data were normalized with the mean of the fold induction of GAPDH, ACTB and CD42B expression and reported as mean ± SD of three experiments (NS = not significant, *P < 0.05; t-test)

Mentions: More importantly, we measured MRP4 and PPARα expression after discontinuation of the drug and we observed a significant decrease of MRP4 and PPARα expression in in vitro studies 2 days after suspension of aspirin treatment (WO 2 days). This effect occured because, 2 days after suspension, about 80% of DAMI cells analyzed were grown in the absence of aspirin. Decrease in MRP4 (Figure 3A) and PPARα (Figure 3B) expression became more evident after 5 and 7 days (WO 5 and WO 7 days).


Aspirin influences megakaryocytic gene expression leading to up-regulation of multidrug resistance protein-4 in human platelets.

Massimi I, Guerriero R, Lotti LV, Lulli V, Borgognone A, Romani F, Barillà F, Gaudio C, Gabbianelli M, Frati L, Pulcinelli FM - Br J Clin Pharmacol (2014)

MRP4 expression after aspirin suspension in DAMI cells. Q-RT-PCR analysis of endogenous MRP4 and PPARα expression in DAMI cells, in either untreated (Ctr) or treated, for 48 h, with 50 μm aspirin (ASA) or after 2, 5 and 7 days of aspirin suspension (wash out, WO). Data were normalized with the mean of the fold induction of GAPDH, ACTB and CD42B expression and reported as mean ± SD of three experiments (NS = not significant, *P < 0.05; t-test)
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4256623&req=5

fig03: MRP4 expression after aspirin suspension in DAMI cells. Q-RT-PCR analysis of endogenous MRP4 and PPARα expression in DAMI cells, in either untreated (Ctr) or treated, for 48 h, with 50 μm aspirin (ASA) or after 2, 5 and 7 days of aspirin suspension (wash out, WO). Data were normalized with the mean of the fold induction of GAPDH, ACTB and CD42B expression and reported as mean ± SD of three experiments (NS = not significant, *P < 0.05; t-test)
Mentions: More importantly, we measured MRP4 and PPARα expression after discontinuation of the drug and we observed a significant decrease of MRP4 and PPARα expression in in vitro studies 2 days after suspension of aspirin treatment (WO 2 days). This effect occured because, 2 days after suspension, about 80% of DAMI cells analyzed were grown in the absence of aspirin. Decrease in MRP4 (Figure 3A) and PPARα (Figure 3B) expression became more evident after 5 and 7 days (WO 5 and WO 7 days).

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.

View Article: PubMed Central - PubMed

Affiliation: Department of Experimental Medicine, Sapienza University of Rome, Rome.

Show MeSH
Related in: MedlinePlus