STATINS-REDOX · Effects of atorvastatin on vascular and myocardial redox state and inflammatory mechanisms in patients with ischemic heart disease

Ischemic heart disease (IHD) is characterised by increased systemic oxidative stress status. Free radicals activate redox sensitive pathways responsible for the production of inflammatory mediators with key role in IHD. Statins have a beneficial role in coronary atherosclerosis, but their potential effect on key features in the pathophysiology of IHD is unclear. In this context, statins may have a beneficial effect in IHD by modifying myocardial and vascular redox signalling. In part A of the study, we will obtain segments of internal mammary arteries (IMA) and saphenous veins (SV) from 60 patients with ischemic heart disease (IHD) undergoing coronary bypass operation. In these vessels we will evaluate the direct effect of atorvastatin on the main sources of superoxide (O2-) radicals generation (uncoupled nitric oxide synthase (NOS) and NADPH-oxidase), by using an ex-vivo setup. We will also investigate the direct effect of atorvastatin on the expression of adipokines (cytokines with important paracrine/endocrine role in IHD) in different types of adipose tissue. We will also examine the individual effect of each adipokine on vascular redox state and signalling. In part B of the study, 60 patients with IHD will be randomised to receive atorvastatin 40mg/d (n=30) or placebo (n=30) for 7 days before their bypass operation. The effect of atorvastatin treatment on endothelial function will be examined by ultrasound in the brachial artery. The effect of atorvastatin on redox signalling (O2- and ONOO- radicals) and inflammatory pathways in myocardium, vascular wall, and human adipose tissue will also be evaluated. This will be the first study examining the effects of atorvastatin on redox state and the activation of redox-sensitive pathways in vascular wall and myocardium of patients with IHD. This study may provide the basis for the design of new clinical trials examining the effect of statins on clinical outcome of patients with IHD.