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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 expression in megakaryocytes. (A) Q-RT-PCR analysis of endogenous MRP4 and PPARα expression in MKs, derived from HPC grown, in mock culture (Ctr), and grown the presence of either 50 μm aspirin (ASA) or 1 μm PPARα agonist, WY14643 (WY). Data were normalized with GAPDH expression and reported as mean ± SD of three experiments **P < 0.01; t-test). (B) Densitometric analysis of MRP4 protein expression in platelets derived from culture grown MKs in mock culture (Ctr) and in the presence of either 50 μm aspirin (ASA) or 1 μm PPARα agonist, WY14643 (WY). Data, normalized with actin expression, were reported as mean of fold increase ± SD, compared with Ctr (n = 3; *P < 0.05; t-test)
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fig05: Aspirin stimulates endogenous MRP4 expression in megakaryocytes. (A) Q-RT-PCR analysis of endogenous MRP4 and PPARα expression in MKs, derived from HPC grown, in mock culture (Ctr), and grown the presence of either 50 μm aspirin (ASA) or 1 μm PPARα agonist, WY14643 (WY). Data were normalized with GAPDH expression and reported as mean ± SD of three experiments **P < 0.01; t-test). (B) Densitometric analysis of MRP4 protein expression in platelets derived from culture grown MKs in mock culture (Ctr) and in the presence of either 50 μm aspirin (ASA) or 1 μm PPARα agonist, WY14643 (WY). Data, normalized with actin expression, were reported as mean of fold increase ± SD, compared with Ctr (n = 3; *P < 0.05; t-test)

Mentions: The results demonstrated that in mature MKs both aspirin and WY14643 increased the mRNA expression of MRP4 (1.7 and 1.8 fold increase, respectively) and PPARα (1.8 and 2.6 fold increase, respectively) as compared with mock culture (Figure 5A). In derived platelets, obtained at the end of the MK culture, treated with either aspirin or WY14643, protein analysis showed an increased MRP4 expression (1.6 fold for aspirin and 1.5 fold for WY14643) as compared with mock culture, suggesting that the effect of MK aspirin and WY14643 treatment persists in platelet progeny (Figure 5B).


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 expression in megakaryocytes. (A) Q-RT-PCR analysis of endogenous MRP4 and PPARα expression in MKs, derived from HPC grown, in mock culture (Ctr), and grown the presence of either 50 μm aspirin (ASA) or 1 μm PPARα agonist, WY14643 (WY). Data were normalized with GAPDH expression and reported as mean ± SD of three experiments **P < 0.01; t-test). (B) Densitometric analysis of MRP4 protein expression in platelets derived from culture grown MKs in mock culture (Ctr) and in the presence of either 50 μm aspirin (ASA) or 1 μm PPARα agonist, WY14643 (WY). Data, normalized with actin expression, were reported as mean of fold increase ± SD, compared with Ctr (n = 3; *P < 0.05; t-test)
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig05: Aspirin stimulates endogenous MRP4 expression in megakaryocytes. (A) Q-RT-PCR analysis of endogenous MRP4 and PPARα expression in MKs, derived from HPC grown, in mock culture (Ctr), and grown the presence of either 50 μm aspirin (ASA) or 1 μm PPARα agonist, WY14643 (WY). Data were normalized with GAPDH expression and reported as mean ± SD of three experiments **P < 0.01; t-test). (B) Densitometric analysis of MRP4 protein expression in platelets derived from culture grown MKs in mock culture (Ctr) and in the presence of either 50 μm aspirin (ASA) or 1 μm PPARα agonist, WY14643 (WY). Data, normalized with actin expression, were reported as mean of fold increase ± SD, compared with Ctr (n = 3; *P < 0.05; t-test)
Mentions: The results demonstrated that in mature MKs both aspirin and WY14643 increased the mRNA expression of MRP4 (1.7 and 1.8 fold increase, respectively) and PPARα (1.8 and 2.6 fold increase, respectively) as compared with mock culture (Figure 5A). In derived platelets, obtained at the end of the MK culture, treated with either aspirin or WY14643, protein analysis showed an increased MRP4 expression (1.6 fold for aspirin and 1.5 fold for WY14643) as compared with mock culture, suggesting that the effect of MK aspirin and WY14643 treatment persists in platelet progeny (Figure 5B).

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