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Inhibition of NAD(P)H Oxidase Attenuates Aggregation of Platelets from High‐risk Cardiac Patients with Aspirin Resistance
Author(s) -
Stef Gyorgyi,
Csiszar Anna,
Xiangmin Zhao,
Ferdinandy Peter,
Veress Gabor,
Ungvari Zoltan
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.a1126-c
Subject(s) - apocynin , nad(p)h oxidase , nad+ kinase , platelet , aspirin , epinephrine , chemistry , oxidase test , nadph oxidase , pharmacology , adenosine diphosphate , superoxide , biochemistry , medicine , platelet aggregation , endocrinology , enzyme
Up to 20% 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 ADP (5 and 10 μmol/L), collagen (2 μg/mL) and epinephrine (10 μmol/L) in the absence and presence of the NAD(P)H oxidase inhibitors DPI and apocynin 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 effects 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 inhibited 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. (Grant support: AHA 0430108N, 0435140N, NIH HL077256).