Inhibition of NAD(P)H oxidase attenuates aggregation of platelets from high-risk cardiac patients with aspirin resistance

Gyorgyi Stef, Anna Csiszar, Zhao Xiangmin, Peter Ferdinandy, Zoltan Ungvari, Gabor Veress

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Up to one-third of serious vascular events in high-risk patients is attributable to a failure of aspirin (ASA) to suppress platelet aggregation. We hypothesized that inhibition of NAD(P)H oxidase may inhibit aggregation of platelets from ASA-resistant (ASA-R) patients. Thus, platelet-rich plasma was isolated from ASA-sensitive (ASA-S) and ASA-R patients (aspirin resistance was defined as higher than expected aggregation to collagen and epinephrine [≥ 40%] after chronic oral treatment with 100 mg/day ASA). Aggregation to adenosine diphosphate (ADP) (5 and 10 μmo1/1), collagen (2 μ/ml) and epinephrine (10 μmol/1) in the absence and presence of the NAD(P)H oxidase inhibitors: diphenylene iodonium (DPI) (1 μmol/1) and apocynin (3 × 10-1 mol/1) was measured by optical aggregometry. Maximal aggregation of ASA-R platelets to collagen and epinephrine was significantly decreased by DPI and apocynin, whereas they had no effect in ASA-S platelets. Maximal aggregation to ADP was unaffected by NAD(P)H oxidase inhibition in either group. In ASA-R platelets both NADPH-driven O2- production (lucigenin chemiluminescence assay) and expression of gp91phox and p67phox subunits of the NADPH oxidase (Western blotting) tended to increase. Collectively, inhibition of NAD(P)H oxidase effectively suppressed collagen and epinephrine-induced aggregation of platelets from ASA-R patients, which may represent a novel pharmacological target for cardioprotection in high-risk cardiac patients.

Original languageEnglish
Pages (from-to)428-436
Number of pages9
JournalPharmacological Reports
Volume59
Issue number4
Publication statusPublished - Oct 16 2007

Keywords

  • Coronary artery disease
  • Myocardial infarction
  • NADPH oxidase
  • Oxidative stress
  • Thrombocyte
  • Thrombosis

ASJC Scopus subject areas

  • Pharmacology

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