RESULTS We identified miR-100 as a potent suppressor of endothelial adhesion molecule expression, resulting in attenuated leukocyte- endothelial interaction in vitro and in vivo as shown by flow cytom- etry and intravital imaging. Mechanistically, miR-100 directly repressed several components of mammalian target of rapamycin complex 1-signaling, including mammalian target of rapamycin and raptor, which resulted in a stimulation of endothelial autophagy and attenuated nuclear factor kB signaling in vitro and in vivo. Pharma- cological inhibition of miR-100 resulted in enhanced plaque lesion formation and a higher macrophage content of the plaque, whereas a systemic miR-100 replacement therapy had protective effects and attenuated atherogenesis, resulting in a decrease of plaque area by 45%. Finally, analysis of miR-100 expression in >70 samples obtained during carotid endarterectomy revealed that local miR-100 expression was inversely correlated with inflammatory cell content in patients. CONCLUSIONS In summary, we describe an anti-inflammatory func- tion of miR-100 in the vascular response to injury and inflammation and identify an important novel modulator of mammalian target of rapamycin signaling and autophagy in the vascular system. Our findings of miR-100 as a potential protective anti-athero-miR suggest that the therapeutic replacement of this microRNA could be a poten- tial strategy for the treatment of chronic inflammatory diseases, such as atherosclerosis, in the future. GW29-e1530 ENaC channel regulation by cholesterol among the microstructures of renal collecting duct epithelial cell membrane Yujia Zhai, Wenbo Qu, Shuainan Mu, Bingchen Liu Department of Cardiology, the Fourth Affiliated Hospital, Harbin Medical University, Harbin, Heilongjiang, China OBJECTIVES The epithelial sodium channel (ENaC) in cortical col- lecting duct (CCD) principal cells plays a critical role in regulating systemic blood pressure. We have previously shown that cholesterol (Cho) in the apical cell membrane regulates ENaC; however, the un- derlying mechanism remains unclear. METHODS Patch-clamp technique and confocal microscopy were used to evaluate ENaC activity and density. RESULTS Here we show that extraction of membrane Cho with methyl-b-cyclodextrin (MbCD) significantly reduced amiloride-sensi- tive current and ENaC single-channel activity. The effects were reproduced by inhibition of Cho synthesis in the cells with lovastatin. We have previously shown that phosphatidylinositol-4,5-bisphos- phate (PIP 2 ), an ENaC activator, is predominantly located in the microvilli, a specialized apical membrane domain. Here, our confocal microscopy data show that a-ENaC was co-localized with PIP 2 in the microvilli and that Cho was also co-localized with PIP 2 in the micro- villi. Either extraction of Cho with MbCD or inhibition of Cho syn- thesis with lovastatin consistently reduced the levels of Cho, PIP 2 , and ENaC in the microvilli. CONCLUSIONS Since PIP 2 can directly stimulate ENaC and also affect ENaC trafficking, these data suggest that depletion of Cho reduces ENaC apical density and activity at least in part by decreasing PIP 2 in the microvilli. GW29-e1537 A novel polymorphism of the APLP2 gene is associated with coronary artery disease in Han population in China Yinghong Wang, Fen Liu, Yining Yang, Zhenyan Fu, Xiang Xie, Yitong Ma Department of Cardiology, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, China OBJECTIVES Elevated serum low-density lipoprotein cholesterol (LDL-C) is a well known risk factor for coronary artery disease (CAD). Several studies have hypothesized that low-density lipoprotein re- ceptor (LDLR), Amyloid precursor protein (APP) or amyloid precursor- like protein 2 (APLP2) may independently mediate Proprotein Con- vertase Subtilisin/Kexin type 9 (PCSK9) endocytosis. The aim of this study was to evaluate the association between APLP2 gene poly- morphisms and CAD. METHODS Two independent case control studies including Han (549 CAD patients and 465 control subjects) and Uygur group (400 CAD patients and 372 control subjects) to study the relevance between the APLP2 single nucleotide polymorphism (SNP), rs2054247 and lesion of coronary artery. RESULTS Among participants in the Han group, there was a signifi- cant difference in the distribution of rs2054247 genotypes between patients with CAD and control groups (P¼0.040). Additionally, the distribution of the dominant model (GG vs. AA þ AG) and the additive model (AG vs. GGþAA) as well as the allele frequency of rs2054247 was significantly different between patients with CAD and control subjects (P ¼ 0.011, P ¼ 0.048, and P ¼ 0.007, respectively). Moreover, the differences remained statistically significant following multivar- iate adjustment ((Total: Odd Ratio(OR) ¼ 1.404, 95% Confidence Interval(CI): 1.05w1.87, P ¼ 0.022; females: OR ¼ 1.903, 95% CI:1.12w3.21, P ¼ 0.016)). CONCLUSIONS This research indicated that rs2054247 could be a novel polymorphism of the APLP2 gene that is associated with CAD in Han Chinese males. GW29-e1539 Dab2 gene variants are associated with coronary artery disease risk in the Chinese Han population Yinghong Wang, Fen Liu, Zhenyan Fu, Yining Yang, Xiang Xie, Chunfang Shan, Bangdang Chen, Yitong Ma Department of Cardiology, the First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, China OBJECTIVES Disabled-2 (Dab2) is a clathrin and cargo binding endo- cytic adaptor protein and cell biology studies revealed that Dab2 plays a role in cellular trafficking of a number of transmembrane receptors and signaling proteins. However, little to nothing is known about its involvement or significance in coronary artery disease (CAD) in Chi- nese populations. METHODS Therefore, we investigated the association between Dab2 single nucleotide polymorphisms (SNPs) and CAD risk in a case-con- trol study including the a Han population (621 CAD patients and 611 control subjects) and the a Uygur population (346 CAD patients and 405 control subjects). All CAD patients and controls were genotyped for the same four SNPs (rs1050903, rs2855512, rs11959928 and rs2255280) of the Dab2 gene with an improved multiplex ligase detection reaction (iMLDR) method. Odds ratios (ORs) and 95% con- fidence intervals (CIs) were estimated by logistic regression. RESULTS After multivariate adjustment in the total Han Chinese population, we found that the rs2855512 A allele and rs2255280 A allele were risk alleles; individuals with the AA genotype had an OR of 1.439 (95% CI: 1.101–1.88, P¼0.008, rs2855512) and 1.416 (95% CI: 1.083–1.85, P¼0.011, rs2255280) for CAD compared with individuals with the AC or CC genotype, respectively. CONCLUSIONS Our data indicated that the AA genotype of rs2855512 and rs2255280 in the Dab2 gene may be a genetic marker of CAD risk. GW29-e1547 Nonhuman disease model in researches of cardiac ion channel dysfunction Chaojun Wang, Pan Li Changhai Hospital of the Second Military Medical University, Shanghai, China OBJECTIVES As many cardiac diseases have a substrate of abnormal cardiac ion channel function, there is an increasing attention to the cardiac ion channel dysfunction. An appropriate and reliable disease model is essential to improving our understanding of the patho- physiology of cardiac ion channel disease, as well as drug safety and effectiveness evaluation, or therapy optimization or personalization. This review focused on the currently used cardiac electrophysiology models, aiming to provide an overlook of the strengths and weak- nesses of the various models, thus provide an aid to researchers when selecting an appropriate model. METHODS Medline and Embase were searched for studies concerned cardiac ion channel dysfunction between 2015 and 2018. 1366 articles were searched and 388 were excluded. Finally, our systematic liter- ature review identified 978 researches and reviews about the re- searches of cardiac ion channel dysfunction. RESULTS Cardiac electrophysiology models have a range from single- cell, tissue, to the whole heart and include both in vitro and in vivo models, thus providing multi-scale disease models for reseachers. HEK293 cell, which were transfected in cardiac ion channel genes is the most widely used single cell model. Recently, induced pluripotent stem cell-cardiomyocytes (iPSC-CMs) which can eliminates the con- founding of the species-specific and inter-personal variations has drawn a rising attention, thus ultimately pave the way for the JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY, VOL. 72, NO. 16, SUPPL S, 2018 C47