Copyright © 2016 Wolters Kluwer Health, Inc. All rights reserved. Abstracts e549 Copyright © 2016 Wolters Kluwer Health, Inc. All rights reserved T H U R S D A Y O R A L LBOS 02-01 HYPERTENSION, ALDOSTERONE AND EPC- MEDIATED ENDOTHALIAL INJURY REPAIR Jun Tao. Department of Hypertension and Vascular Disease, The First Affiliated Hospital, Sun Yat-Sen University, China Objective: Hyperaldosteronemia exerts adverse effects on vascular endothelium except enhanceing blood pressure; however, the impacts and molecular mecha- nisms of hyperaldosteronemia on endothelial progenitor cell (EPC)-mediated en- dothelial repair are yet to be determined. The aim of this study was to investigate the endothelial repair capacity of EPCs from hypertensive patients with primary hyperaldosteronemia (PHA). Design and Method: In vivo endothelial repair capacity of EPCs from PHAs (n = 20), age- and blood pressure-matched essential hypertension patients (n = 20), and age-matched healthy subjects (n = 20) was evaluated by transplantation into nude mice with carotid artery denudation injury. Endothelial function was evalu- ated by flow-mediated dilation of brachial artery in human subjects. Results: In vivo endothelial repair capacity of EPCs and flow-mediated dilation were impaired both in PHAs and in essential hypertension patients; however, the EPC in vivo endothelial repair capacity and flow-mediated dilation of PHAs were declined more seriously than essential hypertension patients. Oral spironolactone improved EPC in vivo endothelial repair capacity and flow-mediated dilation of PHAs. Increased oxidative stress, oxidative 5,6,7,8-tetrahydrobiopterin degra- dation, endothelial nitric oxide synthase uncoupling and decreased nitric oxide production were found in EPCs from PHAs. Nicotinamide adenine dinucleotide phosphate oxidase subunit p47(phox) knockdown or 5,6,7,8-tetrahydrobiopterin supplementation attenuated endothelial nitric oxide synthase uncoupling and en- hanced in vivo endothelial repair capacity of EPCs from PHAs. Conclusions: The present study demonstrated PHAs exhibited more impaired endothelial repair capacity of EPCs than did essential hypertension patients in- dependent of blood pressure, which was related with mineralocorticoid receptor- dependent oxidative stress and subsequently 5,6,7,8-tetrahydrobiopterin degrada- tion and endothelial nitric oxide synthase uncoupling. LBOS 02-02 TELMISARTAN REDUCING MONOCYTE MITOCHONDRIA RESPIRATORY FUNCTION IS ASSOCIATED WITH INHIBITION OF TRANSIENT RECEPTOR POTENTIAL CHANNEL CANONICAL TYPE 3 CHANNELS IN HYPERTENSIVE RATS Daoyan Liu. Department of Hypertension and Endocrinology, Third Military Medical Universit, China Objective: Increased transient receptor potential canonical type 3 (TRPC3) chan- nels have been observed in essential hypertensive patients and spontaneously hy- pertensive rats (SHR). Our previous study shows that mitochondrial respiratory dysfunctions of blood mononuclear cells link with cardiac disturbance in patients with early-stage heart failure. Telmisartan has beneficial effect on both hyperten- sion and metabolic syndrome. In the present study we tested the hypothesis that telmisartan administration inhibited mitochondrial respiratory function was as- sociated with decreased TRPC3 function in monocytes from genetic hypertensive rats (SHR). Design and Method: We treated SHR and normotensive Wistar-Kyoto rats (WKYs) by telmisartan (5 mg/kg/day) for 3 months. The plasma levels of Lp- PLA2, VCAM-1, SEL-P, SEL-E, MCP-1 were measured by ELISA. Mitochon- drial membrane potential changes and mitochondrial ROS production was quanti- fied. Mitochondrial respiratory function was analyzed in a respirometer. Proteins were identified by immunoblotting. Results: H 2 O 2 -induced calcium influx was significantly elevated in monocytes from SHR compared to WKY. After TRPC3 knockdown, H 2 O 2 -induced calcium influx was significantly reduced, but overexpress TRPC3 significantly increased H 2 O 2 -induced calcium influx in monocytes from SHR compared to WKY. Long- term administration of telmisartan significantly reduced increased plasma levels of Lp-PLA2, VCAM-1, SEL-P, SEL-E and MCP-1 in SHR compared to WKY. Telmisartan and TRPC3 knockdown significantly attenuated, but over-expression of TRPC3 elevated the H 2 O 2 -induced mitochondrial ROS production. Mitochon- drial respiratory function of monocyte was significantly increased in SHR com- pared to WKY. Chronic telmisartan treatment decreased monocytes mitochon- drial respiratory function parameters. The expression of hexokinase1 (HXK1) and HXK2, a primary initiator of glycolysis, were significantly reduced in monocytes from SHR compared to WKY. Telmisartan increased HXK1 and HXK2 expres- sion of monocytes from SHR. Conclusions: Mitochondrial respiratory dysfunction of monocyte is associated with increased TRPC3 channels in genetic hypertension. Long-term of telmisar- tan inhibits increased mitochondria respiratory function of monocyte in SHR rats through a hexokinases-dependent pathway. LBOS 02-03 THE INFILTRATING MACROPHAGE-SECRETED GALECTIN-3 PLAYS AN ESSENTIAL ROLE IN CARDIAC FIBROSIS AND DIASTOLIC FUNCTION IN MURINE PRESSURE-OVERLOAD MODEL Jin-jer Chen 1 , Wen-Rui Hao 2 , Kuan-Cheng Chang 1 , Ju-Chi Liu 2 . 1 Department of Internal Medicine, China Medical University Hospital, Taiwan, 2 Division of Cardiology, Department of Medicine, Taipei Medical University Shuang Ho Hos- pital, Taiwan Objective: Cardiac fibrosis is the major pathophysiological process, contributing to the development of diastolic heart failure. We examine the role of macrophage- derived galectin-3 (gal-3) in cardiac fibrosis and diastolic function in response to transverse aortic constriction (TAC). Design and Method: wild-type (WT) and gal-3 knock-out (KO) mice subjected to TAC; immunohistochemistry for myocardial macrophage infiltration,gal-3,and CTGF (connective tissue growth factor) expression; picrosirius red stain for myo- cardial fibrosis; FACS flow- cytometry for defining the origin of myocardial mac- rophages. MTT and Brdu incorporation for cell proliferation; flow-cytometry for cell differentiation; co-immunoprecipitation and confocal microscopy for lectin- carbohydrate interaction and co-localization respectively; echocardiography for left ventricular function. Results: WT mice after TAC showed significant increase of myocardial macro- phage infiltration, gal-3 and CTGF expression, fibroblast proliferation/differen- tiation, and interstitial fibrosis leading to diastolic dysfunction, compared with controls (n = 10, p < 0.01). FACS flow-cytometry further identified that the increased myocardial macrophage population contains predominantly MHC-II low CCR2+ monocytes and MHC-II high CCR2+ monocyte-derived macrophages. Macrophage depletion or gal-3 Knock-out mice markedly suppressed myocar- dial fibrosis. Re-administration of macrophages restored the fibrosis. In in-vitro, confocal microscopy and co-immunoprecipitation confirmed co-localization and gal-3-EGFR interaction on cell membrane. Treatment with recombinant gal-3 in- creased EGFR and downstream ERK phosphorylation, and CTGF expression in wild-type or gal-3 knock-down fibroblasts. Moreover, using MTT and Brdu incor- poration assays, addition of gal-3, or macrophage-derived supernatant, or co-cul- ture with macrophages significantly promoted fibroblast proliferation via CTGF expression. Finally, administration of gal-3 neutralizing monoclonal antibody re- markably reversed the myocardial fibrosis and improved diastolic function. Conclusions: Pressure-overload promotes myocardial macrophage infiltration and the macrophage -secreted gal-3 cross-links with its glycoconjugate, EGFR, resulting in its autophosphorylation, activation of subsequent mitogenic ERK signaling, myocardial CTGF expression, fibroblast proliferation/differentiation, resulting in myocardial fibrosis and diastolic dysfunction. Our findings provide molecular basis for gal-3 as a promising therapeutic target in heart failure. LBOS 02-04 BLOOD PRESSURE-ASSOCIATED POLYMORPHISMS IN SLC4A7 (SODIUM/ BICARBONATE CO-TRANSPORTER NBCN1) ARE LINKED TO GENE EXPRESSION AND INTRACELLULAR PH REGULATION Fu Liang Ng 1 , Ebbe Boedtkjer 2 , Shu Ye 3 , Mark Caulfield 1 . 1 Department of Clinical Pharmacology, William Harvey Research Institute, United Kingdom, 2 Department of Biomedicine, Aarhus University, Denmark, 3 Department of Cardiovascular Sci- ences, University Of Leicester, United Kingdom Objective: Chromosome 3p24.1 containing the SLC4A7 gene has been identi- fied by genome-wide association studies as one of the genomic loci that influ- ence blood pressure. SLC4A7 encodes electroneutral Na + /HCO 3 – co-transporter LATE BREAKING ORAL SESSION 02