Copyright © 2016 Wolters Kluwer Health, Inc. All rights reserved. Abstracts e155 Investigación Biomédica Sant Pau (IIB Sant Pau), Barcelona, SPAIN, 6 Epithe- lial Systems Biology Laboratory, National Heart Lung and Blood Institute (NIH), Bethesda, USA, 7 Laboratori de Proteòmica CSIC/UAB, Instituto de Investigacio- nes Biomédicas de Barcelona (IIBB-CSIC-IDIBAPS), Barcelona, SPAIN, 8 Anax- omics Biotech SL, Barcelona, SPAIN Objective: Diabetic nephropathy (DN) is the major cause of end-stage renal dis- ease. Renin-angiotensin system (RAS) inhibition is the preferred treatment to slow its progression. We have studied the urinary proteomes of patients with DN (high albuminuria) to investigate the pathophysiology of renal disease and iden- tify disease markers and predictors of clinical outcome. Design and method: We included diabetic men with (n = 9) and without DN (n = 12) (control cohort). Data collection included clinical and laboratory evalua- tion of blood and urine at baseline (control cohort and DN-basal), and in patients with DN after 3 months of losartan treatment (DN-treated). Urinary proteome was analyzed and quantified by Tandem Mass Tag (TMT) labeling on a LTQ-Orbitrap mass spectrometer. Results: Patients enrolled in the study showed no differences regarding basic clinical parameters. Urinary proteome analysis have identified 166 differentially excreted proteins when comparing the proteomes of controls and DN patients, 27 comparing DN-treated and DN-basal patients, and 182 among patients DN- treated and controls. Systems biology approach comprising functional proteomic networks and artificial neural networks (TPMS technology) have identified 80 key proteins involved in the pathophysiology of DN and 15 key proteins involved in the efficacy of losartan. There are 7 proteins identified in the urine proteome that are essential in both DN pathophysiology and treatment efficacy. Vascular cell adhesion molecule-1 (VCAM-1) and the angiotensin-metabolizing neutral endo- peptidase neprilysin (NEP) stand out from the other identified proteins because they are the only ones that are DN effectors. They are differentially expressed in the urinary proteome and are also key proteins in both DN pathophysiology and RAS inhibition efficacy. Conclusions: NEP is a membrane-bound zinc-containing metalloproteinase showing great abundance in the brush border of proximal renal tubular cells. NEP is responsible for the processing and catabolism of several vasoactive peptides including angiotensin II and endothelin which may explain its pathogenic role in the development of DN. PP.07.07 CIRCULATING MICROVESICLES (C-MVS) LEVELS AND ENDOTHELIAL FUNCTION IN PATIENTS WITH MULTIFOCAL FIBROMUSCULAR DYSPLASIA (FMD): A CROSS-SECTIONAL STUDY X. Loyer 1 , H. Kettab 2 , A. Lorthioir 2 , M. Frank 2 , R. Niarra 2 , J.M. Renard 1 , Y. Chambon 2 , X. Jeunemaitre 1 , P.F. Plouin 2 , L. Amar 2 , P. Boutouyrie 2 , C.M. Boulanger 1 , M. Azizi 2 . 1 INSERM U970, Paris Cardiovascular Research Center, PARCC, Paris, FRANCE, 2 APHP, Clinical Investigation Center, Departments of Genetics, Pharmacology and Hypertension Unit, HEGP, Paris, FRANCE Objective: FMD is an idiopathic, segmental, non-atherosclerotic non-inflam- matory arterial disease of unknown origin which occurs mostly in middle-aged women and affects medium-sized arteries (renal and carotid arteries in particu- lar). The objective of the study was to identify new hemodynamic and biological biomarkers of the pathology. We investigated i) the flow-mediated dilation (FD) and endothelium-independent dilation (ED) of the brachial artery (BA); ii) c-MVs from different vascular cell origins. Design and method: We conducted a cross sectional study with 50 patients with multifocal FMD, 50 essential hypertensive (EH) patients matched for age, sex, ethnicity and BP and 50 healthy subjects (HS) matched for age, sex and ethnic- ity. Exclusion criteria were: tobacco consumption, hypercholesterolemia, diabe- tes, aspirin or statin treatment. We measured blind to the phenotype: 1) changes in BA diameter after release of hand ischemia (FD) and glyceryl trinitrate (ED) by high-resolution radiofrequency-based echotracking system; and 2) endothelial and smooth-cell derived MVs plasma concentrations by flow cytometry analysis of human platelet free plasma. Results: FMD, EH and HS were well matched. FMD and EH had signifi- cantly higher SBP than HS despite antihypertensive treatments. Circulat- ing levels of total MVs (annexinV+MVs), endothelial MVs (CD144+MVs, CD62E+MVs and CD31+CD41-MVs), CD11a+MVs and smooth muscle derived MVs (SMA (smooth muscle actin)+ MVs) displayed large between- subject variability within each group and did not significantly differ between groups. FD or ED changes in BA diameter did not significantly differ be- tween groups. Conclusions: In conclusion, we could not identify specific changes in c-MVs levels of endothelial or smooth muscle origin in patients with FMD when com- pared with age-, sex-, and ethnicity-matched patients with EH or HS. This result is consistent with the similar acute vasodilatory responses to flow and glyceryl trini- trate observed in FMD patients compared to EH and HS. Taken all together, these results demonstrate that endothelial function is not affected in patients with FMD. PP.07.08 METABOLOMIC STUDY OF PATHWAYS UNDERLYING HEXADECANEDIOATE INDUCED BLOOD PRESSURE ELEVATION N. Alharbi, M.W. McBride, D. Graham, S. Padmanabhan. Institute of Cardiovas- cular and Medical Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UNITED KINGDOM Objective: A putative novel pathway for blood pressure regulation involving the dicarboxylic acid hexadecanedioate was identified in a study associating blood pressure and mortality outcomes with fasting blood metabolites. The functional role of hexadecanedioate on blood pressure elevation and vascular reactivity was confirmed by oral administration of hexadecanedioic acid to Wistar Kyoto (WKY) rats. This study aimed to characterize the metabolic effects of hexadecanedioic acid administration in WKY rats to identify metabolic pathways underlying hexa- decanedioate-induced blood pressure elevation. Design and method: Eleven-week-old male WKY were treated orally with hexa- decanedioic acid (250 mg/kg per day; n = 5) or vehicle (n = 5) for 3 weeks. At sacrifice tissues (aorta, heart, brain, adipose, kidney, and liver) were harvested and global metabolic profiles analysed by UPLC-MS/MS (Metabolon). Data was analysed using random forest classification and the top rank metabolites were highlighted for further investigation. Results: Treatment with hexadecanedioic acid increased hexadecanedioate levels in all tissues tested except the brain, potentially reflecting poor diffusion through the blood-brain barrier. Random Forest (RF) classification of metabolites gave a predic- tive accuracy of 80% for heart and 100% for kidney. The RF Importance Plot of the 30 top-ranking metabolites indicates key differences in lipid, carbohydrate and amino acid metabolism. In heart, increased fatty acids (e.g. acylcarnitines, complex lipids, and lysolipids) in treated rats suggest impairment of fatty acid beta-oxidation. Heart also demonstrated elevated levels of glycogen breakdown products indicat- ing increased glucose demand. In contrast, kidneys demonstrated an increase in long-chain fatty acids and ketone body beta-hydroxybutyric acid, and a decrease in maloylcarnitine suggesting increased beta-oxidative use. In adipose tissue dicarbox- ylate fatty acids (tetradecanedioate and octadecanedioate) were elevated suggesting hexadecandioic acid caused a decrease in beta-oxidation and a shift towards use of peroxisomal omega-oxidation. In liver, hexadecanedioic acid increased cysteine- glutathione disulfide levels suggesting an enhanced oxidising environment. Conclusions: Exogenous administration of hexadecanedioic acid in addition to increasing blood pressure impacts a number of metabolic readouts including changes related to lipid and glucose metabolism and redox homeostasis. These pathways are putative targets for further research to elucidate the mechanism by which hexadecanedioate affects blood pressure. PP.07.09 GENETIC RISK SCORE AND CARDIOVASCULAR COMPLICATIONS IN PATIENTS WITH HYPERTENSION M. Wirtwein 1 , O. Melander 2 , M. Sjogren 2 , M. Hoffmann 3 , K. Narkiewicz 3 , M. Gruchala 4 , W. Sobiczewski. 1 Medical University of Gdansk, Department of Pharmacology, Gdansk, POLAND, 2 Lund University, Department of Clinical