title: Oxidative stress-induced isoprostane formation may contribute to aspirin resistance in platelets.
abstract: Recent studies suggest that aggregation of platelets from patients with coronary artery and cerebrovascular disease may be resistant to low-dose aspirin (ASA) treatment, which may promote plaque-associated thrombus formation. However, the underlying mechanisms of platelet ASA resistance are poorly understood. ASA is thought to inhibit platelet aggregation primarily by inactivating the cyclooxygenase (COX), thus decreasing the synthesis of the pro-aggregatory arachidonic acid metabolite thromboxane A(2) (TxA(2)). However, recent studies also identified a non-enzymatic, oxidation-dependent pathway for the synthesis of the arachidonic acid derivative isoprostanes, which exhibit potent vasoconstrictor and pro-aggregatory effects similar to that of TxA(2). Because the pathophysiological conditions that promote arteriosclerotic vascular diseases (e.g. hypercholesterolemia, diabetes, hyperhomocysteinemia) are thought to be associated with an increased formation of reactive oxygen species and increased plasma isoprostane levels, it can be hypothesized that increased COX-independent isoprostane formation in platelets contribute to ASA resistance.
authors.affiliation: Department of Pathophysiology, Semmelweis University, Budapest, Hungary.
authors.forename: A
authors.initials: A
authors.lastname: Csiszar
authors.forename: G
authors.initials: G
authors.lastname: Stef
authors.forename: P
authors.initials: P
authors.lastname: Pacher
authors.forename: Z
authors.initials: Z
authors.lastname: Ungvari
mesh_terms: D001161:Arteriosclerosis / Q000503:physiopathology; D001241:Aspirin / Q000494:pharmacology*; D001792:Blood Platelets / Q000166:cytology / Q000187:drug effects*; D004351:Drug Resistance; D006801:Humans; D028421:Isoprostanes / Q000096:biosynthesis* / Q000097:blood; D018384:Oxidative Stress / Q000187:drug effects; D010974:Platelet Aggregation / Q000187:drug effects / Q000502:physiology*; D012307:Risk Factors
chemical_list: D028421:Isoprostanes; D001241:Aspirin