Decreased plasma endogenous soluble RAGE, and enhanced adipokine secretion, oxidative stress and platelet/coagulative activation identify non-alcoholic fatty liver disease among patients with familial combined hyperlipidemia and/or metabolic syndrome

• DOI: 10.1016/j.vph.2015.04.004
• Publication Date: 2015-06-25T09:49:12Z
• Authors: Francesca Santilli; Patrizia Blardi; Carlo Scapellato; Monica Bocchia; Gianni Guazzi; Lucia Terzuoli; Antonella Tabucchi; Antonella Silvietti; Benedetta Lucani; Walter Renato Gio...; Francesca Scarpini; Francesca Fazio; Giovanni Davì; Luca Puccetti
• Keywords: Atherothrombosis; CD40/CD40L; esRAGE; FCHL; Metabolic syndrome; NAFLD; Pharmacology; Molecular Medicine; Physiology; Blood Platelets; Male; 0301 basic medicine; Physiology; CD40 Ligand; Receptor for Advanced Glycation End Products; Hyperlipidemia, Familial Combined; esRAGE; FCHL; metabolic syndrome; NAFLD; atherotrombosis; CD40/CD40L.; 03 medical and health sciences; Adipokines; Non-alcoholic Fatty Liver Disease; NAFLD; Humans; Longitudinal Studies; Blood Coagulation; Pharmacology; Metabolic Syndrome; 0303 health sciences; Atherothrombosis; CD40/CD40L; esRAGE; FCHL; Metabolic syndrome; NAFLD; Adipokines; Adiponectin; Advanced Glycosylation End Product-Specific Receptor; Blood Coagulation; Blood Platelets; CD40 Ligand; Cross-Sectional Studies; Female; Humans; Hyperlipidemia, Familial Combined; Interleukin-10; Lipoproteins, LDL; Longitudinal Studies; Male; Metabolic Syndrome X; Middle Aged; Non-alcoholic Fatty Liver Disease; Oxidative Stress; Platelet Activation; Thrombin; Physiology; Molecular Medicine; Pharmacology; Thrombin; Atherothrombosi; CD40/CD40L; Middle Aged; Platelet Activation; Metabolic syndrome; esRAGE; Interleukin-10; 3. Good health; Lipoproteins, LDL; Oxidative Stress; Cross-Sectional Studies; 13. Climate action; FCHL; Molecular Medicine; Female; Adiponectin

In patients with familial combined hyperlipidemia (FCHL), without metabolic syndrome (MS), occurrence of non-alcoholic fatty liver disease (NAFLD) is related to a specific pro-inflammatory profile, influenced by genetic traits, involved in oxidative stress and adipokine secretion. Among FCHL or MS patients, hyperactivity of the ligand-receptor for advanced glycation-end-products (RAGE) pathway, as reflected by inadequate protective response by the endogenous secretory (es)RAGE, in concert with genetic predisposition, may identify those with NAFLD even before and regardless of MS.We cross-sectionally compared 60 patients with vs. 50 without NAFLD. Each group included patients with FCHL alone, MS alone, and FCHL plus MS.NAFLD patients had significantly lower plasma esRAGE, IL-10 and adiponectin, and higher CD40 ligand, endogenous thrombin potential and oxidized LDL. The effects of MS plus FCHL were additive. The genotypic cluster including LOX-1 IVS4-14A plus ADIPO 45GG and 256 GT/GG plus IL-10 10-1082G, together with higher esRAGE levels highly discriminate FCHL and MS patients not developing NAFLD.Among FCHL or MS patients, noncarriers of the protective genotypic cluster, with lower esRAGE and higher degree of atherothrombotic abnormalities coincide with the diagnosis of NAFLD. This suggests an interplay between genotype, adipokine secretion, oxidative stress and platelet/coagulative activation, accelerating NAFLD occurrence as a proxy for cardiovascular disease.