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Lysosomal acid lipase (LAL) hydrolyzes cholesteryl esters (CEs) and triglycerides (TGs) to free cholesterol (FC) and free fatty acids (FFAs), which are then used for metabolic purposes in the cell. The process also occurs in immune cells that adapt their metabolic machinery to cope with the different energetic requirements associated with cell activation, proliferation, and polarization. LAL deficiency (LALD) causes severe lipid accumulation and affects the immunometabolic signature in animal models. In humans, LAL deficiency is associated with a peculiar clinical immune phenotype, secondary hemophagocytic lymphohistiocytosis. These observations suggest that LAL might play an important role in cellular immunometabolic modulation, and availability of an effective enzyme replacement strategy makes LAL an attractive target to rewire the metabolic machinery of immune cells beyond its role in controlling cellular lipid metabolism.

s / Atherosclerosis 241 (2015) e32ee71 e35 EC4-Fc over-expression significantly increased the incidence of severe AAA compared to controls (50% vs. 28%). Medial proliferation (measured by PCNA) was significantly reduced in MMP7-/EC4-Fc mice compared to controls (2.5±0.3% vs. 0.5±0.06%), but there was no significant difference in the rate of apoptosis between the groups. In vitro, treatment with MMP7 inhibitor and EC4-Fc also significantly reduced human aortic VSMC proliferation (4.2±0.9% and 2.7±0.4% vs. 8.1±0.9%, n1⁄44). Conclusions: Combined inhibition of MMP7 and EC4 over-expression increased aneurysm severity at least in part by inhibition of proliferation and repair. EAS-0722. PI3K-C2B PLAYS A KEY ROLE IN THE ACTIVATION AND THE PROLIFERATION OF T LYMPHOCYTES: IMPACT ON VASCULAR DISEASES G. Balzarotti , G. Tibolla , F. Bonacina , C. D'Alonzo , A. Dhyani , M. Falasca , G.D. Norata , A. Catapano . Dipartimento di Scienze Farmacologiche e Biomolecolari, Universit a degli Studi di Milano, Milano, Italy; Blizard Institute, Queen Mary University, London, United Kingdom Aim: Circulating effector memory T cells (TEM) are associated with atherosclerosis and coronary artery disease in humans and in animal models. Phosphoinositide3-kinases (PI3Ks) are involved in many important aspects of immune cell development, differentation and function and contribute to T lymphocytes biological responses. In this context the role of the class II enzyme isoform b (PI3K-C2b) is debated and available data suggest that this PI3K regulates naive T lymphocytes (T0) activation by modulating the intermediate K+ channel KCa3.1, crucial for sustained Ca++ entry. Aim of this study was to characterize the role of PI3K-C2b in the context of T cell polarization. Methods/results: Blood, lymphnodes and spleenof PI3K-C2bknockoutmice were analysed by flow cytometry and a significant reduction in memory T cells, both central and effector, in blood, spleen and lymph nodes from PI3KC2b deficient mice compared to wild-type littermates was observed (circulating naive-memory T cells: 71,36% -27,50% vs 79,30%-17,01% for wild type and PI3K-C2b KO mice respectively, p1⁄40,02 and p1⁄40,004). To assess if PI3KC2b plays a role in T cells proliferation, we perform a proliferation assay on lymphocytes derived fromwild type and PI3K-C2b null mice, using the CFSE staining.Weobservedasignificant reduction inPI3K-C2bKOTcells (mainly in CD4+) compared to T cells from control mice. Conclusion: This results suggest that PI3K-C2b is involved in T cells maturation and proliferation and further studies are needed to validate the therapeutic potential of PI3K-C2b inhibition for the treatment of cardiovascular and immune diseases. EAS-0731. ASSOCIATION BETWEEN INFLAMMATION MARKERS AND ABDOMINAL AORTIC CALCIFICATION IN PATIENTS WITH PERIPHERAL ARTERIAL DISEASE V. Zelinskiy , A. Zhorina , V. Andreev . Cardiovascular Surgery, NorthWestern State Medical University named after I.I. Mechnikov, SaintPetersburg, Russia; CT e Imaging, North-Western State Medical University named after I.I. Mechnikov, Saint-Petersburg, Russia; Cardiovascular surgery, North-Western State Medical University named after I.I. Mechnikov, Saint-Petersburg, Russia Aim: The relationship between inflammation and vascular calcification in patients with peripheral arterial disease (PAD) is unclear. The goal of our research work was to assess the association between inflammation markers (fibrinogen, C-reactive protein (CRP), von Willebrand factor (vWf), total and differential types of leukocyte count) and abdominal aortic calcification (AAC) in patients with PAD. Methods: A total of 1800 patients with PAD were examined. PAD was defined as an ABI