Inhibition of NAD(P)H oxidase attenuates aggregation of platelets from high-risk cardiac patients with aspirin resistance
| Autor: | Zoltan Ungvari, Péter Ferdinandy, Gabor Veress, Gyorgyi Stef, Anna Csiszar, Zhao Xiangmin |
|---|---|
| Rok vydání: | 2007 |
| Předmět: |
Male
Heart Diseases Platelet Aggregation Platelet Function Tests Blotting Western Drug Resistance Administration Oral Pharmacology Biochemistry chemistry.chemical_compound Onium Compounds Genetics medicine Humans Platelet Enzyme Inhibitors Molecular Biology Aged Oxidase test NADPH oxidase Membrane Glycoproteins biology Aspirin Dose-Response Relationship Drug Chemistry Platelet-Rich Plasma Acetophenones NADPH Oxidases Middle Aged Phosphoproteins Adenosine Diphosphate Adenosine diphosphate Epinephrine NAD(P)H oxidase Apocynin Luminescent Measurements NADPH Oxidase 2 biology.protein Female NAD+ kinase Collagen Biotechnology medicine.drug |
| Zdroj: | Pharmacological reports : PR. 59(4) |
| ISSN: | 1734-1140 |
| Popis: | 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 [or = 40%] after chronic oral treatment with 100 mg/day ASA). Aggregation to adenosine diphosphate (ADP) (5 and 10 micromol/l), collagen (2 microg/ml) and epinephrine (10 micromol/l) in the absence and presence of the NAD(P)H oxidase inhibitors: diphenylene iodonium (DPI) (1 micromol/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 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. |
| Databáze: | OpenAIRE |
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