30: High density lipoprotein reduces the human monocyte inflammatory response through ATP-binding cassette transporter A1

Multiple Risk Factors in Cardiovascular Disease—Abstracts

cardiomyopathy, borreliosis, rickettsiosis, HIV cardiomyopathy. Noninvasive biomarkers for necrosis include the troponins, for inflammation the IL-cascade and anticardiac antibodies (AMLAs, ASAs, AFAs, BAR-ab). In most cases the diagnosis of dilated cardiomyopathy with or without inflammation will need both non-invasive (echocardiography, CMR) and the invasive biomarkers from the endomyocardial biopsy (EMB). Invasive biomarkers from EMB are a positive PCR for viral or microbial persistence or their exclusion in the case of autoreactive myocarditis and quantitative immunohistology for inflammation. From the international Marburg registry the most frequent viral biomarker is Parvo B19 (28%), followed by HHV6 (7%), EBV (8%), ADV (4%), CMV(4%) and enterovirus(1%) . The diagnosis of inflammation by biopsy is based on the World Heart Federation Criteria of 14 leukocytes /mm² in the biopsy specimen and less frequent than the presence of the microbial agent. In a step-wise approach we will illustrate the diagnosis and finally the treatment options in dilated cardiomyopathies of different origins. Funding: I have been invited to this talk by the Giovanni Lorenzini Foundation

caused a dose-dependent reduction in the activation of monocytic CD11b induced by PMA or receptor-dependent agonists. The constituent of HDL responsible for the anti-inflammatory effects on CD11b activation was found to be apoA-I. Cyclodextrin, but not cyclodextrin/cholesterol complex, also inhibited PMA-induced CD11b activation implicating cholesterol efflux as the main mechanism. This finding was further confirmed using the apoA-I mimetic peptide L37PA, previously demonstrated to efflux cholesterol. The blockade of ABCA1 with a specific anti-ABCA1 antibody abolished the effect of apoA-I. Anti-inflammatory effects of apoA-I and HDL were also observed in functional models including cell adhesion to an endothelial cell monolayer and monocytic spreading under shearflow along with transmigration, the effects were eliminated after blocking ABCA1. Our definitive assay on monocytes derived from a Tangier disease patient or from unaffected and heterozygous relatives also demonstrated the key requirement for ABCA1. Conclusions: This work demonstrates that the anti-inflammatory effects of HDL on monocytes is dependent on apolipoprotein A-I (apoA-I) and cholesterol efflux via the ABCA1. Funding: NHMRC

30 HIGH DENSITY LIPOPROTEIN REDUCES THE HUMAN MONOCYTE INFLAMMATORY RESPONSE THROUGH ATP-BINDING CASSETTE TRANSPORTER A1 D. Sviridov1, A. Murphy1, K. Woolard1, A. Hoang1, N. Mukhamedova1, R. Stizaker2, S. McCormick3, A. Remaley4, J. Chin-Dusting1. 1Baker Heart Research Institute, Melbourne, Australia, 2Walter and Elisa Hall Institute for Medical Research, Melbourne, Australia, 3 University of Otago, Dunedin, New Zealand, 4 National Heart, Lung and Blood Institute, Bethesda, MD, USA Objective: The anti-inflammatory effects of high density lipoprotein (HDL) on endothelial cells are established; however such effects on another partner in inflammation, monocytes, are less studied. Methods: Human monocytes were isolated from human blood followed by assessment of CD11b activation/expression and cell adhesion under shear-flow. Results: HDL

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31 C-REACTIVE PROTEIN PREDICTS FUNCTIONAL STATUS AND CORRELATES WITH LEFT VENTRICULAR EJECTION FRACTION IN PATIENTS WITH CHRONIC STABLE ANGINA P. Avanzas1, R. Arroyo-Espliguero2, J. Quiles3, J. C. Kaski4. 1Hospital Universitario Central de Asturias. Area del Corazon, Oviedo, Spain, 2Hospital Universitario de Guadalajara, Department of Cardiology, Guadalajara, Spain, 3Hospital de San Juan, Department of Cardiology, Alicante, Spain, 4St. George´s Hospital, University of London, London, United Kingdom Objective: C-reactive protein (CRP) is not merely an inflammatory marker but may also participate in the pathogenesis of atherosclerosis and myocardial injury. We sought to investigate the relationship among CRP, left ventricular ejection fraction (LVEF) and symptoms of congestive heart failure (CHF) in patients with chronic stable