PI3K-C2B plays a key role in the activation and the proliferation of t lymphocytes: Impact on vascular diseases

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<0.9 in at least 1 leg. The occurrence of AAC was obtained in 504 (28%) patients with PAD (381 (76%) male and 123 (24%) female) without diabetes mellitus and chronic renal failure. AAC was detected by CT imaging. Total leukocyte count (TLC), monocyte count, neutrophil count, fibrinogen level, CRP and vWf levels were measured. Control group was included 1296 PAD patients without objective signs of AAC. Results: AAC was strong associated with high monocyte count (p<0.001). Differences in neutrophil count and TLC between groups were not statistically significant (p1⁄40.065). Fibrinogen level, CRP and vWf levels were 7.4±0.8 g/l, 9.7±1.6 mg/l, 186.1±48.2% in the AAC group vs. 4.6±1.2 g/l, 5.6±0.6 mg/l, 99.5±22.6% in the non-AAC group, respectively (p<0.01). Those correlations were significant after adjustment for traditional risk factor of AAC. Conclusion: Our study suggests that inflammation may play an important role in the pathogenesis of aortic calcification. The present study shows that increasing of monocyte count and levels of other serum inflammation markers (fibrinogen, CRP, vWf) are significantly associated with the presence of AAC. EAS-0786. THE EXTENSIBILITY AND ULTIMATE MATERIAL STRENGTH OF ATHEROSCLEROTIC COMPONENT IN HUMAN CAROTID PLAQUES Z. Teng , M. Sutcliffe , Q. Lu , J. Gillard . Department of Radiology, University of Cambridge, Cambridge, United Kingdom; Department of Engineering, University of Cambridge, Cambridge, United Kingdom; Department of Vascular Surger, Changhai Hospital, Shanghai, China Aim: Most cardiovascular ischaemic events are due to atherosclerotic plaque rupture. From an engineering viewpoint, it is due to the mechanical loading induced by blood pressure and flow exceeding its material strength. This study is designed to quantify the extensibility and ultimate material strength of each component within the carotid plaque, including fibrous cap (FC), media, lipid and intraplaque haemorrhage or thrombus (IPH/T). Methods: Twenty-one human endarterectomy carotid plaques were collected. The plaque was cut into rings and different type of atherosclerotic tissue was dissected. In total, 65 media strips from 17 samples, 59 FC strips from 14 samples, 38 lipid strips from 11 samples, and 21 IPH/T strips from 11 samples were obtained and tested by stretching slowly until break. Results: In total, 54.3% FC, 53.6 media, 69.6% lipid, and 56.2% IPH/T strips broke in the central region and data from these strips were pooled for analysis. As shown in the figure, the extreme extensibility of different atherosclerotic tissues is comparable. No significant difference is found in the ultimate strength of FC and media and neither as the lipid and IPH/T. Both FC and media are much stronger than either lipid or IPH/T. Conclusion: The obtained results could serve as a criterion for the mechanics-based plaque vulnerability assessment.