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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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Aspirin stimulates endogenous MRP4 mRNA and protein expression in DAMI cells. (A) Q-RT-PCR analysis of endogenous MRP4 and PPARα expression 48 h after treatment with either 50 μm or 100 μm aspirin (ASA) and/or 1 μm PPARα agonist, WY14643 (WY). Data were normalized with the mean of the fold induction of GAPDH, ACTB and CD42B expression and reported as mean ± SD of three experiments (*P < 0.05, **P < 0.01, ***P < 0.001; t-test). Statistical analysis for the comparison WY14643 vs. WY14643+ASA 50 μm is not significant (NS). (B) Representative Western blot, of four performed, of endogenous MRP4 expression 48 h after treatment with either 50 μm aspirin (ASA) or 1 μm PPARα agonist (WY). Densitometric analysis is reported as mean ± SD of increasing fold, compared to control. (n = 4; *P < 0.05; t-test)
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fig01: Aspirin stimulates endogenous MRP4 mRNA and protein expression in DAMI cells. (A) Q-RT-PCR analysis of endogenous MRP4 and PPARα expression 48 h after treatment with either 50 μm or 100 μm aspirin (ASA) and/or 1 μm PPARα agonist, WY14643 (WY). Data were normalized with the mean of the fold induction of GAPDH, ACTB and CD42B expression and reported as mean ± SD of three experiments (*P < 0.05, **P < 0.01, ***P < 0.001; t-test). Statistical analysis for the comparison WY14643 vs. WY14643+ASA 50 μm is not significant (NS). (B) Representative Western blot, of four performed, of endogenous MRP4 expression 48 h after treatment with either 50 μm aspirin (ASA) or 1 μm PPARα agonist (WY). Densitometric analysis is reported as mean ± SD of increasing fold, compared to control. (n = 4; *P < 0.05; t-test)

Mentions: DAMI cells treated with aspirin (50−100 m for 48 h) showed higher MRP4 mRNA levels compared with mock culture (Figure 1A upper graph).


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)

Aspirin stimulates endogenous MRP4 mRNA and protein expression in DAMI cells. (A) Q-RT-PCR analysis of endogenous MRP4 and PPARα expression 48 h after treatment with either 50 μm or 100 μm aspirin (ASA) and/or 1 μm PPARα agonist, WY14643 (WY). Data were normalized with the mean of the fold induction of GAPDH, ACTB and CD42B expression and reported as mean ± SD of three experiments (*P < 0.05, **P < 0.01, ***P < 0.001; t-test). Statistical analysis for the comparison WY14643 vs. WY14643+ASA 50 μm is not significant (NS). (B) Representative Western blot, of four performed, of endogenous MRP4 expression 48 h after treatment with either 50 μm aspirin (ASA) or 1 μm PPARα agonist (WY). Densitometric analysis is reported as mean ± SD of increasing fold, compared to control. (n = 4; *P < 0.05; t-test)
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig01: Aspirin stimulates endogenous MRP4 mRNA and protein expression in DAMI cells. (A) Q-RT-PCR analysis of endogenous MRP4 and PPARα expression 48 h after treatment with either 50 μm or 100 μm aspirin (ASA) and/or 1 μm PPARα agonist, WY14643 (WY). Data were normalized with the mean of the fold induction of GAPDH, ACTB and CD42B expression and reported as mean ± SD of three experiments (*P < 0.05, **P < 0.01, ***P < 0.001; t-test). Statistical analysis for the comparison WY14643 vs. WY14643+ASA 50 μm is not significant (NS). (B) Representative Western blot, of four performed, of endogenous MRP4 expression 48 h after treatment with either 50 μm aspirin (ASA) or 1 μm PPARα agonist (WY). Densitometric analysis is reported as mean ± SD of increasing fold, compared to control. (n = 4; *P < 0.05; t-test)
Mentions: DAMI cells treated with aspirin (50−100 m for 48 h) showed higher MRP4 mRNA levels compared with mock culture (Figure 1A upper graph).

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