Limits...
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.

Show MeSH

Related in: MedlinePlus

MRP4 expression in healthy volunteer (HV) platelets after aspirin treatment. (A) Q-RT-PCR analysis, MRP4 mRNA level expression in platelets obtained from HV after 1 (T1), 7 (T7) and 15 (T15) days' aspirin treatment (300 mg day−1). Data were normalized with the mean of the fold induction of GAPDH, ACTB and CD42B expression and reported as mean ± SD of 10 experiments using platelets obtained from different HV (NS = not significant, **P < 0.02). (B) Western blot analysis of MRP4 protein expression in platelets obtained from HV treated with aspirin for 1 (T1), 7 (T7) and 15 (T15) days. Densitometric analysis is reported as fold increase, compared with T1. Results are representative of 10 experiments (**P < 0.02; t-test). (C) Immunofluorescence microscopy of platelets obtained from HV treated with aspirin for 1 (T1), 7 (T7) and 15 (T15) days. Platelets were incubated with antibodies against MRP4 (green fluorescence). Representative experiment out of five performed using platelets obtained from different HV. The arrow points to MRP4 plasma membrane localization
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4256623&req=5

fig06: MRP4 expression in healthy volunteer (HV) platelets after aspirin treatment. (A) Q-RT-PCR analysis, MRP4 mRNA level expression in platelets obtained from HV after 1 (T1), 7 (T7) and 15 (T15) days' aspirin treatment (300 mg day−1). Data were normalized with the mean of the fold induction of GAPDH, ACTB and CD42B expression and reported as mean ± SD of 10 experiments using platelets obtained from different HV (NS = not significant, **P < 0.02). (B) Western blot analysis of MRP4 protein expression in platelets obtained from HV treated with aspirin for 1 (T1), 7 (T7) and 15 (T15) days. Densitometric analysis is reported as fold increase, compared with T1. Results are representative of 10 experiments (**P < 0.02; t-test). (C) Immunofluorescence microscopy of platelets obtained from HV treated with aspirin for 1 (T1), 7 (T7) and 15 (T15) days. Platelets were incubated with antibodies against MRP4 (green fluorescence). Representative experiment out of five performed using platelets obtained from different HV. The arrow points to MRP4 plasma membrane localization

Mentions: The results revealed that platelet expression of MRP4 mRNA in HV, increased slightly after 7 days' aspirin treatment and significantly after 15 days' treatment (approximately 30%), as compared with those found in platelets obtained after 1 day's treatment (P = 0.08) (Figure 6A).


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 in healthy volunteer (HV) platelets after aspirin treatment. (A) Q-RT-PCR analysis, MRP4 mRNA level expression in platelets obtained from HV after 1 (T1), 7 (T7) and 15 (T15) days' aspirin treatment (300 mg day−1). Data were normalized with the mean of the fold induction of GAPDH, ACTB and CD42B expression and reported as mean ± SD of 10 experiments using platelets obtained from different HV (NS = not significant, **P < 0.02). (B) Western blot analysis of MRP4 protein expression in platelets obtained from HV treated with aspirin for 1 (T1), 7 (T7) and 15 (T15) days. Densitometric analysis is reported as fold increase, compared with T1. Results are representative of 10 experiments (**P < 0.02; t-test). (C) Immunofluorescence microscopy of platelets obtained from HV treated with aspirin for 1 (T1), 7 (T7) and 15 (T15) days. Platelets were incubated with antibodies against MRP4 (green fluorescence). Representative experiment out of five performed using platelets obtained from different HV. The arrow points to MRP4 plasma membrane localization
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig06: MRP4 expression in healthy volunteer (HV) platelets after aspirin treatment. (A) Q-RT-PCR analysis, MRP4 mRNA level expression in platelets obtained from HV after 1 (T1), 7 (T7) and 15 (T15) days' aspirin treatment (300 mg day−1). Data were normalized with the mean of the fold induction of GAPDH, ACTB and CD42B expression and reported as mean ± SD of 10 experiments using platelets obtained from different HV (NS = not significant, **P < 0.02). (B) Western blot analysis of MRP4 protein expression in platelets obtained from HV treated with aspirin for 1 (T1), 7 (T7) and 15 (T15) days. Densitometric analysis is reported as fold increase, compared with T1. Results are representative of 10 experiments (**P < 0.02; t-test). (C) Immunofluorescence microscopy of platelets obtained from HV treated with aspirin for 1 (T1), 7 (T7) and 15 (T15) days. Platelets were incubated with antibodies against MRP4 (green fluorescence). Representative experiment out of five performed using platelets obtained from different HV. The arrow points to MRP4 plasma membrane localization
Mentions: The results revealed that platelet expression of MRP4 mRNA in HV, increased slightly after 7 days' aspirin treatment and significantly after 15 days' treatment (approximately 30%), as compared with those found in platelets obtained after 1 day's treatment (P = 0.08) (Figure 6A).

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