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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

Flow cytometric determination of white blood cell (WBC) contamination of platelet suspensions. Flow cytometric analysis after staining with antibodies specific for CD61 (PerCP-Cy5-5) and for CD45 (APC-Cy7). In (a), the box includes cellular suspension according to SSC and FSC. In (b) the CD61+/CD45+ events gated on P1 are shown in the right upper quadrant.
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fig1: Flow cytometric determination of white blood cell (WBC) contamination of platelet suspensions. Flow cytometric analysis after staining with antibodies specific for CD61 (PerCP-Cy5-5) and for CD45 (APC-Cy7). In (a), the box includes cellular suspension according to SSC and FSC. In (b) the CD61+/CD45+ events gated on P1 are shown in the right upper quadrant.

Mentions: White blood cells in platelet suspension were identified through their expression of CD45. A volume of 10 μL of platelet suspension was incubated for 20 min in the dark with (1) peridinin chlorophyll protein-cyanin-5.5- (PerCP-Cy5.5-) labelled monoclonal antibodies against human CD61 (Becton Dickinson, San Jose, USA); (2) allophycocyanin-cyanin-7- (APC-Cy7-) labelled monoclonal antibodies against human CD45 (Becton Dickinson, San Jose, USA) (Figure 1).


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)

Flow cytometric determination of white blood cell (WBC) contamination of platelet suspensions. Flow cytometric analysis after staining with antibodies specific for CD61 (PerCP-Cy5-5) and for CD45 (APC-Cy7). In (a), the box includes cellular suspension according to SSC and FSC. In (b) the CD61+/CD45+ events gated on P1 are shown in the right upper quadrant.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4383491&req=5

fig1: Flow cytometric determination of white blood cell (WBC) contamination of platelet suspensions. Flow cytometric analysis after staining with antibodies specific for CD61 (PerCP-Cy5-5) and for CD45 (APC-Cy7). In (a), the box includes cellular suspension according to SSC and FSC. In (b) the CD61+/CD45+ events gated on P1 are shown in the right upper quadrant.
Mentions: White blood cells in platelet suspension were identified through their expression of CD45. A volume of 10 μL of platelet suspension was incubated for 20 min in the dark with (1) peridinin chlorophyll protein-cyanin-5.5- (PerCP-Cy5.5-) labelled monoclonal antibodies against human CD61 (Becton Dickinson, San Jose, USA); (2) allophycocyanin-cyanin-7- (APC-Cy7-) labelled monoclonal antibodies against human CD45 (Becton Dickinson, San Jose, USA) (Figure 1).

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