Inhibition of NAD(P)H oxidase attenuates aggregation of platelets from high-risk cardiac patients with aspirin resistance.
Journal Title: Pharmacological Reports - Year 2007, Vol 59, Issue 4
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 mumol/l), collagen (2 mug/ml) and epinephrine (10 mumol/l) in the absence and presence of the NAD(P)H oxidase inhibitors: diphenylene iodonium (DPI) (1 mumol/l) and apocynin (3 x 10(-4) mol/l) 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 ADPwas unaffected by NAD(P)H oxidase inhibition in either group. In ASA-R platelets both NADPH-driven O(2)(.-) production (lucigenin chemiluminescence assay) and expression of gp91(phox) and p67(phox) 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.
Authors and Affiliations
Gyorgi Stef, Anna Csiszar, Zhao Xiangmin, Peter Ferdinandy, Zoltan Ungvari, Gabor Veress
Keywords
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