Inhibition of nuclear factor-kappa B attenuates atherosclerosis in apoE/LDLR - Double knockout mice

Abstract

Nuclear factor - kappa B (NF-kappa B) is a good therapeutic target for cardiovascular disease and numerous efforts are being made to develop safe NF-kappa B inhibitors. Nowadays many authors address NF-kappa B as a major therapeutic target in atherosclerosis, especially for preventive measures, in the light of two main hypothesis of atherosclerosis: oxidation and inflammation. We hypothesized that ammonium pyrrolidinedithioocarbamate (PDTC) - a well-known inhibitor of NF-kappa B could inhibit the development of atherosclerosis in this experimental model. We used apoE/LDLR - DKO mouse model, which is considered as a one of the best models to study the anti-atherosclerotic effect of drugs. In this model PDTC inhibited atherogenesis, measured both by "en face" method (25,15 +/- 2,9% vs. 15,6 +/- 3 0,6%) and "cross-section" method (565867 +/- 39764 mu m(2) vs. 291695 +/- 30384 mu m(2)). Moreover, PDTC did not change the profile of cholesterol and triglycerides in blood. To our knowledge, this is the first report that shows the effect of PDTC on atherogenesis in gene-targeted apoE/LDLR - double knockout mice.