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PM367

Stable Angina Pectoris And Diabetes Mellitus Of Type 2: The Role Of TheAtherogenic Lipid Profile And Inflammatory Markers

Ludmila Gapon, Tatiana Petelina, Natalia Musikhina, Natalia Dementjeva,Vadim Kuznetsov*Tyumen Cardiology Center, Tyumen, Russian Federation

Introduction: Cardiovascular disease in patients with type 2 diabetes mellitus (DM) as acause of death is a leader in virtually all countries of the world. The risk of coronary arterydisease (CAD) in patients with type 2 DM is 2-4 times higher and the risk of acutemyocardial infarction is 6-10 times higher than in the general population of patients. Thecondition of lipid profile and vascular inflammatory reaction is of great importance whenshaping coronary atherosclerotic stenosis in patients with stable angina pectoris (SAP) andDM of type 2.Objectives: Comparable evaluation of lipid profile and inflammatory markers in patientswith SAP and patients with SAP and DM of type 2.Methods: A total of 97 patients with CAD (mean age 60.3�9.8 years) with nonsignifi-cant coronary stenosis (<75%) were examined. Group I included 33 patients with SAPand DM of type 2, group II consisted of 64 patients with SAP without DM. All patientsreceived statins, ACE inhibitors, beta blockers, dual antiplatelet therapy. In group I allpatients received antihyperglycemic therapy. Lipid profile parameters (total cholesterol,triglycerides, LDL cholesterol, VLDL cholesterol, lipoprotein (a), Apo-A, Apo-B), in-flammatory markers (hs-CRP, TNF-alpha, homocysteine, interleukine 1 b, 6, 8, sCD40 L,MMP-9, TIMP-1), endothelial dysfunction markers (endothelin-1, nitrites) weremeasured.Results: There were high levels of hs-CRP, TNF-alpha, lipoprotein (a), MMP-9, tri-glycerides, and endothelin-1 in both groups. The level of TIMP-1 was significantlyreduced in both groups. Patients in group 1 had significantly elevated levels of totalcholesterol, LDL cholesterol, homocysteine, Apo-B, Apo-B/Apo A-1 ratio, IL -1 b . Ingroup 1 the following positive correlations were found: between glycohemoglobin andApo-B, Apo-B/Apo A-1 ratio, homocysteine, IL -1 b, sCD40 L; IL-6 and hs-CRP; ho-mocysteine and LDL cholesterol, MMP-9, duration of CAD; endothelin-1 and sCD40L,TNF-alpha. It was shown that with an increase of 1 mmol/L in homocysteine level and of1 mg/l in hs–CRP level, the risk of DM in patients with SAP increased by 1.1 and 3.8times, respectively.Conclusion: In patients with type 2 DM there was a significant increase in the levels ofatherogenic lipid fractions as well as homocysteine, hs-CRP and IL-1 b which mayindicate a higher risk of coronary events even in the absence of significant coronarystenosis.Disclosure of Interest: None Declared

PM368

A novel mechanism of hyperhomocysteinemia-promoted leukocyte-endotheliuminteraction

Juan Feng*1, Yuhong Luo1, Haiping Zhao1, Wengong Wang2, Xian Wang11Dept. of Physiology and Pathophysiology, 2Dept. of Biochemistry and Molecular Biology, PekingUniversity Health Science Center, Beijing, China

Introduction: Atherosclerosis is an inflammatory disease with immunoinflammatory re-sponses contributing to disease initiation and progression. The interaction between theendothelium and activated immune cells is an early event in hyperhomocysteinemia(HHcy)-induced vascular injury and atherosclerosis. But the mechanism is still unknown.Objectives: To investigate the effects and possible mechanisms of acute HHcy-inducedleukocyte rolling and adhesion in mouse cerebral venules. Furthermore, we will explore therole of tRNA methyltransferase NSun2 in Hcy-promoted interaction between the endo-thelium and leukocytes.Methods: Male C57 BL⁄6J mice were injected with D.L-Hcy (50 mg⁄kg). The effect of HHcyon the leukocyte rolling and adhesion in cerebral vessels was assessed using intravitalmicroscopy. Plasma cytokines and chemokines were evaluated by cytometric bead array.ROS production in human umbilical vein endothelial cells (HUVECs) was determined byflow cytometry. NSun2 and adhesion molecule expression were investigated by immu-nohistochemistry or western blot. CD18 phosphorylation and the Src⁄PI3K⁄Akt pathway inleukocytes were determined by confocal microscopy and western blot. In co-culture sys-tem, the role of NSun2 in the interaction between leukocytes and HUVECs was alsoinvestigated.Results: HHcy promoted leukocyte rolling and adhesion, ROS production in HUVECs.Plasma KC, MIP-2, and MCP-1 levels were increased significantly by HHcy. E-selectin andICAM-1 expression on cerebrovascular endothelium and CD11b⁄CD18 expression on leu-kocytes were upregulated by HHcy. And Src⁄PI3K⁄Akt pathway mediated the CD18 phos-phorylation in leukocytes. Results of the in vitro experiments have indicated thatHcy increasedthe expression ofNSun2 and ICAM-1 inHUVECs.NSun2 could bind to andmethylate ICAM-1 3’-UTR, thus increased the ICAM-1 expression by enhancing its translation. Knockdown ofNSun2 decreased endothelial ICAM-1 expression and the number of adhered cells.Conclusion: HHcy provoked leukocyte rolling and adhesion in cerebral venules, adhesionmolecule expression and activation, which is related to the Src⁄PI3K⁄Akt pathway in leu-kocytes. NSun2 mediated the upregulated ICAM-1 expression and HUVEC-leukocyteinteraction induced by Hcy. It will provide a new mechanism for Hcy-related inflammationfrom the angle of RNA methylation.Disclosure of Interest: None Declared

e136

PM370

Non-Invasive Molecular Ultrasound Imaging For Monitoring And Efficacy Testing OfTargeted Anti-Thrombotic Agents Using Platelet-Targeted Microbubbles

Xiaowei Wang1, Jan David Hohmann1, Ephraem Leitner1, Ingo Ahrens2, Christoph Hagemeyer1,Karlheinz Peter*11Thrombosis, BakerIDI Heart and Diabetes Institute, Melbourne, Australia, 2Cardiology,Univerisity of Freiburg, Freiburg, Germany

Introduction: Molecular ultrasound imaging offers a non-invasive technology widelyavailable for rapid clinical diagnosis. We tested whether microbubbles (MBs), which areselectively targeted to activated platelets, provide a high-resolution, real-time imaging ofthrombosis and monitoring of thrombolysis.Objectives: We used this approach to evaluate a platelet targeted urokinase plasminogenactivator (targ-scuPA) that is hypothesized to offer anti-thrombolytic potency withoutbleeding complications.Methods: MBs were conjugated to a single-chain antibody specific for an epitope calledLigand Induced Binding Site on activated GPIIb/IIIa (LIBS-MB).Results: LIBS-MBs strongly adhered to immobilized activated platelets and micro-thrombiunder flow. Carotid artery thrombi in mice, induced by ferric chloride, were assessed with ul-trasoundbefore and afterMB injection. Analysis of the thrombus area demonstrated a significantincrease in decibel after LIBS-MB but not after MB injection (p<0.01). After thrombolysis with500U/g BW of commercial urokinase (commUPA), LIBS-MB ultrasound imaging allowsmonitoring of the reduction in thrombus size (p<0.001). Similar results were obtained whencomparing the size to grayscale intensity reduction. In addition, 75U/g BW of targ-scuPA issufficient for thrombolysis, whereas 75U/g BW of commUPA or non-targ-scuPA are not(p<0.01). 500U/g BW of commUPA, the concentration required to match the effectiveness of75U/g BW of targ-scuPA, resulted in prolonged tail bleeding time, whereas no increase inbleedingwas observedwhen the equally effectivebut lowerdoseof 75U/gBWscuPA (p<0.001).Conclusion: We are able to demonstrate that our targeted MB specifically bind to activatedplatelets enabling real-time molecular ultrasound imaging of thrombosis and monitoring ofsuccess or failure of thrombolysis in vivo. In an exemplary application a highly promisingclot-targeted thrombolytic drug was shown to provide effective thrombolytic potentialwithout compromising haemostasis.Disclosure of Interest: None Declared

PM371

Prediction of Angiographic Severity of Coronary Artery Disease by Simple BiomarkerA Preliminary Study

Hariman Kristian*1, Benny Setiadi1, Bambang Budiono2, Janry Pangemanan1, Agnes L. Panda1,Reggy Lefrandt11cardiology and vascular medicine, sam ratulangi university, manado, 2cardiology and vascularmedicine, rs awal bros, makassar, Indonesia

Introduction: Consistent relationship between various inflammatory markers and car-diovascular diseases has been established. Neutrophil to lymphocyte ratio (NLR) is aninexpensive, easy to obtain, widely available marker of inflammation, which was associatedwith arterial stiffness and significant markers of cardiovascular disease.Objectives: To analyze the relatonship between NLR and the severity of CAD.Methods: This is a cross sectional study, which include CAD patients who underwentcoronary angiography between January to August 2013. The exclusion criteria includeactive infection,malignancy, and previous coronary intervention. Routine blood testwas done in all patients. NLR and traditional risk factors, including hypertension,type 2 diabetes mellitus, and dyslipidemia were analyzed to identify their relation tothe severity of coronary artery stenosis based on modified gensini score. Statisticalanalyses were done using SPSS 17.0 with P < 0.05 is considered statisticallysignificant.Results: A total 88 patients were included in this study (mean age 57�9 years, meanNLR 2.67�2.05). From these, 72 patients (81.8%) were male. Hypertension, type 2diabetes mellitus and dyslipidemia were found in 64 patients (72.73%), 48 patients(47.73%), and 42 patients (47.73%) respectively. There is a significant relationship be-tween NLR with the modified gensini score (r¼ 0.44, P value <0.001). From multi-variate analysis, NLR is an independent predictor of severe lesion (modified gensini score>13) with OR1.55, P value 0.001. From the Receiver operating curve (ROC) analysis,the most effective cutoff value for NLR to predict severe lesion was 2.87 (sensitivity 75%,specificity 77.6%).Conclusion: There is significant relationship between NLR with the severity of coronaryartery stenosis. NLR is an independent predictor of severe lesion. The most effective cutoffvalue for NLR to predict severe lesion is 2.87. NLR is simple biomarkers which can predictseverity of coronary artery disease.Disclosure of Interest: None Declared

PM372

Cardiomyocytes derived from human embryonic stem cells have a distinctive micro-RNA signature

Deevina Arasaratnam*1, David Elliott1, Anthony White21Cell Biology, Murdoch Childrens Research Institute, 2Medicine, Nursing and Health Sciences,Monash University, Melbourne, Australia

GHEART Vol 9/1S/2014 j March, 2014 j POSTER/2014 WCC Posters