Aspirin resistance in coronary artery disease is correlated to elevated markers for oxidative stress but not to the expression of cyclooxygenase (COX) 1/2, a novel COX-1 polymorphism or the PlA1/2polymorphism

Autor:	Johannes Ruef, Roger Kranzhöfer
Rok vydání:	2006
Předmět:	Blood Platelets medicine.medical_specialty Platelet Aggregation Drug Resistance Single-nucleotide polymorphism Coronary Artery Disease Dinoprost medicine.disease_cause Polymorphism Single Nucleotide Coronary artery disease Lipid peroxidation Thromboxane A2 chemistry.chemical_compound Antigens Neoplasm Nephelometry and Turbidimetry Internal medicine medicine Humans SNP Platelet RNA Messenger Genetics Polymorphism Genetic Aspirin biology business.industry Integrin beta3 Hematology General Medicine medicine.disease Thromboxane B2 Oxidative Stress Endocrinology chemistry Cyclooxygenase 1 biology.protein Lipid Peroxidation Cyclooxygenase business Oxidative stress
Zdroj:	Platelets. 17:163-169
ISSN:	1369-1635 0953-7104
DOI:	10.1080/09537100500441101
Popis:	Aspirin resistance (AR) is estimated to be present in 5-75% of patients and is related to increased cardiovascular mortality. However, the underlying mechanisms are mostly unknown. In the present study, AR was detected in 14 out of 55 patients (25%) with coronary artery disease. The presence of concomitant anti-inflammatory drugs did not affect AR. Plasma levels of thromboxane B(2) as well as the markers for oxidative stress and known platelet activators 8-isoprostane and lipid peroxidation products were significantly higher in aspirin-resistant individuals (349.3 pg/ml, 53.9 pg/ml, and 538 micromol/l) compared to controls (113.7 pg/ml, 10.3 pg/ml, and 32.2 micromol/l; P0.05, respectively). Platelet cyclooxygenase-1 (COX-1) and COX-2 mRNA and protein expression were without significant differences between the two groups. DNA sequencing detected a novel platelet COX-1 single nucleotide polymorphism (SNP) resulting in amino acid exchange at position 8 (Arg8/Trp8). The wild-type as well as the heterozygous and homozygous SNP were present in both patient groups without significant differences. The aspirin binding (Arg120) and acetylation site (Ser529) were unaffected in the samples tested. Neither was AR related to the platelet integrin PlA(1)/A(2) polymorphism. In conclusion, AR appears to be unrelated to differences in platelet COX-1 and COX-2 expression or to a novel platelet COX-1 SNP and the PlA(1)/A(2) SNP. However, a correlation exists to elevated eicosanoids generated by oxidative stress indicating COX-1-independent pathways for the generation of platelet activating molecules represent a potential cause for AR.
Databáze:	OpenAIRE
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