Abstract 15197: Lipopolysaccharide-Nuclear Factor-kappa B Pathway and Lipoprotein Apheresis Effects in Patients With Familial Hypercholesterolemia and Coronary Artery Disease

Abstract

Introduction: Inflammation may play an important role in atherosclerosis in familial hypercholesterolemia (FH). Lipopolysaccharide (LPS)-nuclear factor-kappa B (NF-κB) pathway is a routine signal process activated in inflammatory status. Hypothesis: We assessed the hypothesis that LPS-NF-κB axis is markedly activated and lipoprotein apheresis has an inhibitory effect on this pathway in patients with FH and coronary artery disease (CAD). Methods: In this matched case-control study a genetically diagnosed FH cohort who presented stable CAD (n=63) was compared with 63 non-FH CAD and 63 non-FH non-CAD controls matched by sex and age. Plasma LPS levels and NF-κB activity were compared among the three groups. In addition, we studied in vitro LPS-induced interleukin-6 production by mononuclear cells from 16 FH cases without previous statin use and compared them with their respective matched control groups. Subsequently, these 16 FH patients underwent lipoprotein apheresis. Blood samples were taken immediately before and regularly after apheresis for measuring LPS and NF-κB. Results: FH plus CAD had higher LPS levels and NF-κB activity than CAD and non-CAD controls (all p <0.01). LPS-induced interleukin-6 production by mononuclear cells of FH plus CAD was also much higher compared with CAD and non-CAD controls (both p <0.01). Moreover, plasma LPS levels ( p <0.001) and NF-κB activity ( p <0.01) were dramatically reduced after apheresis in FH patients. Conclusions: In conclusion, genetically confirmed FH patients with CAD had a marked activation of LPS-NF-κB axis, while lipoprotein apheresis significantly attenuated this key inflammatory pathway, suggesting that inflammation may be an important therapeutic target for FH patients.