Conclusions: These results, even if partial and preliminary, suggest that miRNAs represent not only the essential players in the pathogenesis of the disease, but also potential therapeutic targets to modulate with specific drugs to restore and correct the dysregulated gene expression of those proteins involved in the pathophysiologic processes of PA. Correct those miRNAs expressed in an aberrant manner is equivalent to stopping the disease process, and e in some cases e even to reverse it, by acting, at various levels, on gene expression of several elements involved in the development of the disease and improving patient's clinical conditions. MICROBIOTA COMPOSITION AFFECTS LIPID METABOLISM AND INTESTINAL HOMEOSTASIS M. Busnelli 1 , S. Manzini 1 , A. Boukadiri 2 , A. Bruneau 3 , C. Philippe 3 , P. G erard 3 , G. Chiesa 1 . 1 Dipartimento di Scienze Farmacologiche e Biomolecolari, Universit a degli Studi di Milano, Milano, Italy; 2 Institut National de la Recherche Agronomique, UMR1313 G en etique Animale et Biologie Int egrative, Jouy-en-Josas, France; 3 Institut National de la Recherche Agronomique, UMR1319 Microbiologie de l'alimentation au service de la sant e, Jouy-en-Josas, France E-mail address: marco.busnelli@gmail.com (M. Busnelli). Undernutrition, defined as inadequate intake or assimilation of nutri- ents, still determines worldwide half of all deaths in children younger than 5 years of age. Protein-energy malnutrition is currently the most important nutri- tional problem in most low-income countries and leads to a wide range of continuing health and developmental problems. Protein-energy malnutrition is characterized by stunted growth, hepatic steatosis and a damaged gut mucosal architecture, associated with malabsorption, impaired mucosal permeability and inflammation. Nowadays, it is widely recognized that the intestinal content, such as dietary constituents and commensal bacteria, influences physiological and pathological processes throughout the body. The mammalian gastrointestinal tract harbors trillions of microbes that belong to all three domains of life (Bacteria, Archaea, and Eukarya) and their viruses, the so-called gut microbiota. An increasing number of clinical and preclinical studies indicate that food is a critical factor that influences the composition of the gut microbial community and that the micro- biota, in turn, can influence the efficiency of energy harvesting from ingested food. The microbiota modulates the bioavailability and meta- bolism of macro- and micronutrients as well as metabolites, including bile acids, lipids, amino acids, vitamins and short-chain fatty acids. This study was aimed at determining whether different microbiota can limit the devastating effects of a protein-deficient diet by modulating energy extraction and availability from food. To this aim, germ-free mice were colonized with different microbiota communities obtained from mice eating different diets. Germ-free mice are those born and reared without exposure to any live microbes. To obtain microbiota donors, Specific-Pathogen-Free male 8-week-old C57BL/6 mice were fed for 5 weeks a chow diet (CD), a high-fat diet (HFD), or a low-protein diet (LPD). Gut microbiota transfer in germ- free mice was performed by harvesting cecal contents from donor mice and introducing them, by gavage, into 5-week-old germ-free male C57Bl/6 recipient mice, maintained in separate, sterile isolators. Even though body weight at the end of the experimental period was unaffected by different microbiota consortia, subsequent analyses indicated that: i) germ-free mice receiving the CD microbiota were more prone to develop hepatic steatosis; ii) germ-free mice receiving the HFD microbiota had an increased concentration of plasma phos- pholipids and a different caecal composition in terms of short chain fatty acids, with an increased percentage of Propionate and a reduced percentage of Butyrate. In addition, the intestine showed shortened villi and cypts, both in the small intestine and in the colon. These histological modifications were accompanied by a robustly upregu- lated expression of Duox2 and Duoxa2, indicative of a perturbed in- testinal mucosal homeostasis; iii) germ-free mice receiving the LPD microbiota had an increased plasma concentration of HDL-cholesterol. To clarify this finding, the expression of a wide panel of genes related to lipid/lipoprotein metabolism is currently under investigation. In conclusion, the results obtained clearly indicate that different microbiota are able to modulate plasma lipid levels and the accumu- lation of lipids in the liver parenchyma leading to steatosis. Additionally, the microbiota shaped by a high-fat diet severely modifies the histo- logical architecture of the gut and the intestinal expression of genes indicative of an increased microbiota/mucosa interaction, reflecting an altered microbiota composition or a defective host defense mechanism. SEVERE CAROTID ATHEROMATOUS STENOSIS REGRESSION AFTER SUBCUTANEOUS ADMINISTRATION OF TOCILIZUMAB V. Cairo MD, A. Lo Gullo MD, C.O. Aragona MD, F. Savarino MD, F. Mamone MD, M. Scuruchi PhD, M.A. Sardo MD, E. Imbalzano MD, M. Cinquegrani MD, G. Mandraffino MD, PhD, A. Saitta MD. Department of Clinical and Experimental Medicine, University of Messina, Italy E-mail address: gmandraffinomd@libero.it (G. Mandraffino). Takayasu arteritis (TA) is a chronic inflammatory disease of unknown etiology that involves large and medium-sized arteries, primarily the aorta and its major branches. TA is a therapeutic challenge because corticosteroids and conventional immunosuppressive agents are not always safe and/or efficacious. Interleukin 6 (IL-6) has emerged as a key cytokine in the pathogenesis of TA and its serum levels have been shown to well correlate with disease activity. We report the case of a normotensive, normolipemic 19 years old female patient with TA refractory to conventional immunosuppres- sive agents successfully treated by subcutaneous administration of tocilizumab. The follow-up period was 3.6 years. At the first evalua- tion, despite the current use of prednisone at dosage of (50 mg/Kg/ day), the patients presented with high clinical indices of disease ac- tivity, and high inflammatory markers; moreover, at the age of 22 years old, ultrasonography doppler scan diagnosed a severe athero- matous carotid involvement, with estimated stenosis of 75 %, bilat- erally; after tocilizumab was started, the patient was clinically and instrumentally evaluated every 16 weeks, and a progressive normalization of clinical and bio-humoral indices of disease was observed (stably normal since the 5th month of treatment); predni- sone dosage could be consistently tapered and finally stopped since the 4th month of treatment. At the last US evaluation (6th month of treatment), carotid stenosis were estimated as 45%, bilaterally. At 12th month since the treatment has been started the carotid stenosis has been estimated lower than 25%, bilaterally. No significant side effects have been reported, and the patient is continuing to take the drug. Subcutaneous administration of tocilizumab appears a good option in refractory TA with an effective steroid-sparing effect. In addition, it seems to have very favorable effects on endothelial function improving cIMT, and significantly reducing artery hypertrophy. ALIROCUMAB IN HIGH CARDIOVASCULAR RISK PATIENTS WITH HETEROZYGOUS FAMILIAL HYPERCHOLESTEROLEMIA: EFFICACY AND SAFETY IN LIPID LOWERING LEVELS I. Calcaterra, F. Jossa, G. Marotta, M. Gentile, M.N. Di Minno, B. De Simone, V. Mallardo, P. Rubba. Department of Clinical Medicine & Surgery, University “Federico II” Medical School, Naples, Italy E-mail address: ileniacalcaterra@hotmail.it (I. Calcaterra). Background: Many patients with Heterozygous Familial Hypercholes- terolemia (FH), at high cardiovascular risk are not at target for Low Density Lipoprotein Cholesterol (LDL-C) levels despite maximal toler- ated traditional treatment. Alirocumab is an anti-protein convertase subtilisin/kexin type 9 (PCSK9) monoclonal antibody, approved for the treatment of hypercholesterolemia. Aim: We investigated the efficacy in lipid lowering and safety of Alir- ocumab in patients with FH. Abstracts the SISA e11