Enhanced NOX-2 derived oxidative stress in offspring of patients with early myocardial infarction.

Offspring of patients with early myocardial infarction have a higher risk to develop cardiovascular events; the underlying physiopathology is still unclear. Several lines of evidence support a role for oxidative stress in atherogenesis and NADPH oxidase-2 (NOX-2) is considered a major source of O2– in human. Furthermore, oxidative stress regulates arachidonic acid metabolism via activation of platelet phospholipase-A2. The aim of this study was to address NOX-2 activity as well as serum thromboxane B2 (TXB2) and 8-isoPGF2-alpha in offspring of patients with premature myocardial infarction. Ninety-two consecutive subjects, including 46 offspring of patients with premature myocardial infarction and 46 healthy subjects (HS) matched for age and gender, were recruited. A cross sectional study was performed to compare serum activity of soluble NOX-2-dp (sNOX-2-dp), blood levels of isoprostanes and serum TXB2 in these two groups. Compared with HS, offspring of patients with early myocardial infarction had higher values of serum TxB2, isoprostanes and sNOX-2-dp. Bivariate analysis in the overall population showed that serum sNOX-2-dp levels were significantly associated with serum isoprostanes and TXB2. A multiple linear regression analysis was performed to define the independent predictors of sNOX-2-dp. Serum isoprostanes (SE: 0.07; standardized coefficient β: 0.579; P < 0.001) and TXB2 levels (SE: 0.06; standardized coefficient β: 0.211; P < 0.001) were significantly associated to sNOX-2-dp (R2: 0.42). This study shows that Nox-2 activation is a key determinant of oxidative stress and platelet activation in offspring of patients with premature myocardial infarction. • Offspring of patients with early myocardial infarction have a higher cardiovascular risk. • NADPH oxidase-generated oxidative stress plays a pivotal role in atherosclerosis. • Nox-2 is determinant for oxidative stress and platelet activation in offspring of patients with early myocardial infarction. [ABSTRACT FROM AUTHOR]