Valutazione in vivo dello stress ossidativo e dell'attivazione piastrinica nell'ipobetalipoproteinemia familiare: confronto con l'ipercolesterolemia familiare e l'iperalfalipoproteinemia familiare

Background Oxidative stress is associated with an increased risk of atherothrombosis and platelet activation as several animal models have been shown. The increased production of reactive oxygen species (ROS) leads to lipids peroxidation of the cell membranes and of lipoproteins, high production of F2-isoprostanes from arachidonic acid, thus modulating the platelet activation induced by thromboxane. 8-iso-PGF2a and 11-deidro-tromboxane (TX)B2 are in vivo markers of oxidative stress and platelet activation, respectively. Recently it has been shown that subjects with low plasma levels of HDL (increased cardiovascular risk) present with high urinary levels of these markers. This excretion is reduced by changing life style and by pharmacological increase of HDL cholesterol. Aim and Methods The aim of this study was to evaluate in a group of FHBL subjects (n=10) the urinary levels of 8-iso-PGF2 and 11-deidro-TX B2 and to compare these finding with ADH (n=10) and HALP subjects (n=10). We have performed also the analysis of plasma markers of inflammation (IL-6), platelet (NOX-2) and endothelial activation (ICAM-1, VCAM-1) to understand the real CV risk in FHBL subjects compared to ADH and HALP patients. Results The analysis of oxidative stress, platelet and endothelial activation markers didn’t show any significant difference between FHBL and HALP subjects. Non-treated ADH exhibit higher urinary secretion of F2-isoprostanes and plasma levels of NOX-2, ICAM-1, VCAM-1 and IL-6 than FHBL and HALP subjects. After lipid lowering treatment, ADH subjects exhibit a significant decrease of all these markers. Conclusions These data confirm a linear correlation between the excretion of rates of F2-isoprostanes and subjects at high CV risk (such ADH subjects). Several limitations include small sample size of our study population. These findings may have important clinical implications for primary and secondary prevention in ADH and HALP subjects underlying possible benefits of low cholesterol plasmatic levels in FHBL subjects.