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Inflammatory and antioxidant pattern unbalance in "clopidogrel-resistant" patients during acute coronary syndrome.

Caruso R, Rocchiccioli S, Gori AM, Cecchettini A, Giusti B, Parodi G, Cozzi L, Marcucci R, Parolini M, Romagnuolo I, Citti L, Abbate R, Parodi O - Mediators Inflamm. (2015)

Bottom Line: Eight (28%) out of 29 ACS patients resulted NR to clopidogrel.In R patients the proinflammatory cytokine IL-6 decreased, while the anti-inflammatory cytokine IL-1Ra increased.Proinflammatory milieu persists in nonresponders for a long time after the acute event while antioxidant blood factors tend to conform to normal responsiveness.

View Article: PubMed Central - PubMed

Affiliation: National Research Council, Institute of Clinical Physiology, Cardiothoracic and Vascular Department, Niguarda Ca' Granda Hospital, Piazza Ospedale Maggiore 3, 20162 Milan, Italy.

ABSTRACT

Background: In acute coronary syndrome (ACS), inflammation and redox response are associated with increased residual platelet reactivity (RPR) on clopidogrel therapy. We investigated whether clopidogrel interaction affects platelet function and modulates factors related to inflammation and oxidation in ACS patients differently responding to clopidogrel.

Material and methods: Platelet aggregation was measured in 29 ACS patients on dual (aspirin/clopidogrel) antiplatelet therapy. Nonresponders (NR) were defined as RPR ≥70% by ADP. Several inflammatory and redox parameters were assayed and platelet proteome was determined.

Results: Eight (28%) out of 29 ACS patients resulted NR to clopidogrel. At 24 hours, the levels of Th2-type cytokines IL-4, IFNγ, and MCP-1 were higher in NR, while blood GSH (r-GSHbl) levels were lower in NR than responders (R). Proteomic analysis evidenced an upregulated level of platelet adhesion molecule, CD226, and a downregulation of the antioxidant peroxiredoxin-4. In R patients the proinflammatory cytokine IL-6 decreased, while the anti-inflammatory cytokine IL-1Ra increased.

Conclusions: In patients with high RPR on clopidogrel therapy, an unbalance of inflammatory factors, platelet adhesion molecules, and circulatory and platelet antioxidant molecules was observed during the acute phase. Proinflammatory milieu persists in nonresponders for a long time after the acute event while antioxidant blood factors tend to conform to normal responsiveness.

No MeSH data available.


Related in: MedlinePlus

Profile of levels of IL-6 (a), IL-1ra (b), and IL-4 (c) in NR and R patients (R: empty box-plots; NR: dark box-plots). P for time refers to time-dependent changes (24 hours, 1 week, and 1 month) in groups assessed by nonparametric Friedman test, *P < 0.025 versus 24 hrs by Bonferroni adjusted post hoc test for pairwise comparisons.
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fig2: Profile of levels of IL-6 (a), IL-1ra (b), and IL-4 (c) in NR and R patients (R: empty box-plots; NR: dark box-plots). P for time refers to time-dependent changes (24 hours, 1 week, and 1 month) in groups assessed by nonparametric Friedman test, *P < 0.025 versus 24 hrs by Bonferroni adjusted post hoc test for pairwise comparisons.

Mentions: Follow-up evaluation of inflammatory and redox profiles was assessed in 19 ACS patients (24 hours, one week, and one month after clopidogrel loading dose). In NR, the levels of inflammatory parameters were unchanged during the first month after dual antiplatelet therapy administration, with the exception of IL-6 that tended to decrease after one week from the acute phase. At variance, R patients showed significant changes of IL-6, IL-1ra, and IL-4 levels over time (Figure 2).


Inflammatory and antioxidant pattern unbalance in "clopidogrel-resistant" patients during acute coronary syndrome.

Caruso R, Rocchiccioli S, Gori AM, Cecchettini A, Giusti B, Parodi G, Cozzi L, Marcucci R, Parolini M, Romagnuolo I, Citti L, Abbate R, Parodi O - Mediators Inflamm. (2015)

Profile of levels of IL-6 (a), IL-1ra (b), and IL-4 (c) in NR and R patients (R: empty box-plots; NR: dark box-plots). P for time refers to time-dependent changes (24 hours, 1 week, and 1 month) in groups assessed by nonparametric Friedman test, *P < 0.025 versus 24 hrs by Bonferroni adjusted post hoc test for pairwise comparisons.
© Copyright Policy - open-access
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4383491&req=5

fig2: Profile of levels of IL-6 (a), IL-1ra (b), and IL-4 (c) in NR and R patients (R: empty box-plots; NR: dark box-plots). P for time refers to time-dependent changes (24 hours, 1 week, and 1 month) in groups assessed by nonparametric Friedman test, *P < 0.025 versus 24 hrs by Bonferroni adjusted post hoc test for pairwise comparisons.
Mentions: Follow-up evaluation of inflammatory and redox profiles was assessed in 19 ACS patients (24 hours, one week, and one month after clopidogrel loading dose). In NR, the levels of inflammatory parameters were unchanged during the first month after dual antiplatelet therapy administration, with the exception of IL-6 that tended to decrease after one week from the acute phase. At variance, R patients showed significant changes of IL-6, IL-1ra, and IL-4 levels over time (Figure 2).

Bottom Line: Eight (28%) out of 29 ACS patients resulted NR to clopidogrel.In R patients the proinflammatory cytokine IL-6 decreased, while the anti-inflammatory cytokine IL-1Ra increased.Proinflammatory milieu persists in nonresponders for a long time after the acute event while antioxidant blood factors tend to conform to normal responsiveness.

View Article: PubMed Central - PubMed

Affiliation: National Research Council, Institute of Clinical Physiology, Cardiothoracic and Vascular Department, Niguarda Ca' Granda Hospital, Piazza Ospedale Maggiore 3, 20162 Milan, Italy.

ABSTRACT

Background: In acute coronary syndrome (ACS), inflammation and redox response are associated with increased residual platelet reactivity (RPR) on clopidogrel therapy. We investigated whether clopidogrel interaction affects platelet function and modulates factors related to inflammation and oxidation in ACS patients differently responding to clopidogrel.

Material and methods: Platelet aggregation was measured in 29 ACS patients on dual (aspirin/clopidogrel) antiplatelet therapy. Nonresponders (NR) were defined as RPR ≥70% by ADP. Several inflammatory and redox parameters were assayed and platelet proteome was determined.

Results: Eight (28%) out of 29 ACS patients resulted NR to clopidogrel. At 24 hours, the levels of Th2-type cytokines IL-4, IFNγ, and MCP-1 were higher in NR, while blood GSH (r-GSHbl) levels were lower in NR than responders (R). Proteomic analysis evidenced an upregulated level of platelet adhesion molecule, CD226, and a downregulation of the antioxidant peroxiredoxin-4. In R patients the proinflammatory cytokine IL-6 decreased, while the anti-inflammatory cytokine IL-1Ra increased.

Conclusions: In patients with high RPR on clopidogrel therapy, an unbalance of inflammatory factors, platelet adhesion molecules, and circulatory and platelet antioxidant molecules was observed during the acute phase. Proinflammatory milieu persists in nonresponders for a long time after the acute event while antioxidant blood factors tend to conform to normal responsiveness.

No MeSH data available.


Related in: MedlinePlus