2017 Cardiovascular Research Day Abstract Book

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35 Identification of Candidate Long QT Syndrome Type 2 Patients Starting from Exome Sequences Identified in a Biobank Cohort Allison Hall, MS 1 • Don Burgess, PhD 2 • Pierre Fwelo 1 • Jennifer Smith 3 • Corey Anderson, PhD 4 • Craig T. January, MD, PhD 4 • Ann Stepanchick, PhD 4 • Uyenlinh Mirshah, PhD 4 • Jonathan Luo, PhD 4 • Dustin Hartzel, PhD 4 • Michael Murray, MD 5 • Tooraj Mirshahi, PhD 5 • Brian Delisle, PhD 1 1Physiology, University of Kentucky • 2 Physics, Asbury • 3 University of Kentucky • 4 University of Wisconsin • 5 Geisinger Health System Staff Introduction: Every year congenital long QT syndrome (LQTS) is thought to cause sudden cardiac death in hundreds of individuals in the US. Genetic screening potentially could identify LQTS patients before it strikes. However, genetic analyses often find novel rare sequence variants of uncertain physiological significance, and little is known about genetic screening in unaffected populations. Hypothesis: LQTS type 2 (LQT2) is caused by loss-of-function mutations in the rapidly activating delayed rectifier K+ channel gene KCNH2 (Kv11.1). Screening for KCNH2 variants using an approach similar to the Comprehensive In Vitro Proarrhythmia Assay for drug testing will allow the identification of candidate LQT2 patients starting from exome sequences. Methods: Ten KCNH2 mutations from the NCBI ClinVar database listed as “pathogenic”, “suspectedpathogenic”, or “conflicting interpretations” were identified in 10,000 Whole Exome Sequences (WES) from the Geisinger MyCode® cohort. The KCNH2 mutations were screened using Western blot to quantify terminally glycosylated mature Kv11.1 protein (a proxy for Kv11.1 channel trafficking); patch-clamp to measure Kv11.1 channel current (IKv11.1); and computational simulations with a human ventricular action potential (AP) model to predict AP duration (a correlate for the QT interval). Results: Two of the KCNH2 mutations were trafficking-deficient to decrease mature Kv11.1 protein and peak IKv11.1, and five mutations altered normal Kv11.1 channel activation or deactivation. Simulating the decrease in IKv11.1 caused by the trafficking-deficient KCNH2 mutations increased AP duration by >30%, whereas the mutations that disrupted Kv11.1 channel gating did not predict significant changes in AP duration. De-identified Electronic Health Records (EHR) from the Geisinger MyCode® subjects showed that the corrected QT interval (QTc Bazette) for the patients that harbored the trafficking-deficient KCNH2 mutations was ≥480 ms, whereas the average QTc for all EHR database subjects was
36 Optimization of immunomagnetic separation for cryopreserved cord blood and apheresis mononuclear cell fractions derived endothelial progenitor cells Himi Tripathi, PhD 1 • Lakshman Chelvarajan, PhD 1 • Brad J Berron, PhD 2 • Ahmed Abdel Latif, MD, PhD 1 1Gill Heart Institute and Division of <strong>Cardiovascular</strong> Medicine, University of Kentucky • 2 Department of Chemical and Materials Engineering, University of Kentucky Staff Introduction: <strong>Cardiovascular</strong> tissue damage in acute myocardial infarction mainly arises from the loss of blood flow, leading to changes in the composition and function of the ischemic region and heat failure. Multiple studies have examined the utility of CD34+ endothelial progenitor cells (EPCs) for limiting tissue damage and promoting tissue repair after an ischemic event. However, isolation of EPCs using traditional fluorescent activated cell sorting is cumbersome, expensive and time consuming. In this study, we examined the efficacy of novel antigen based methods for EPC isolation from human cord blood. Methods and Results: Immunomagnetic cell sorting protocol to purify CD34+ cells from cryopreserved cord blood and apheresis samples was optimized using MACS ultrapure CD 34 microbead kit. Cell viability, CD 34 purity and endothelial progenitor cells phenotypic expression was assessed using flow cytometer and trypan blue assay. After thawing cryopreserved cord blood, we observed >80 ± 10% viable cells and 95±5% viable apheresis cells. CD34+ purity of 74 ± 16% and 94 ± 1.7% was achieved in cryopreserved cord blood and apheresis samples, respectively. Recovery of CD34+ cells was higher from apheresis (64.6%) in comparison to cord blood (31.3%). Post selection, the expression of EPCs markers was 65.6± 23.2 for CD31 and 90.3 ± 6.6 for CD133 in cord blood and 79.7± 5.5 and 69.6 ± 5.4 in apheresis samples. Additionally, we observed significantly higher recovery and system efficiency when using small input number of CD34+ cells (3.02 ± 2.7 X 106 vs. 31.3% ±54.1 X 106; p
Page 1 and 2: Cardiovascular Research Day ABSTRAC
Page 3 and 4: SCHEDULE FOR THE DAY Friday, Novemb
Page 5 and 6: SCHEDULE FOR THE DAY continued Frid
Page 7 and 8: 2017 GILL HEART INSTITUTE YOUNG INV
Page 9 and 10: FEATURED SPEAKER Calum MacRae, M.D.
Page 11 and 12: SPECIAL PRESENTATION Mark Stoops He
Page 13 and 14: NOTES 12
Page 15 and 16: 2017 POSTER PARTICIPANTS 40 Mohamed
Page 17 and 18: 2017 ABSTRACTS 16
Page 19 and 20: 2 Inhibition of Megalin Reduces Ath
Page 21 and 22: 4 Identification of a Lipid Signatu
Page 23 and 24: 6 Serum Amyloid A Activates the NLR
Page 25 and 26: 8 Azithromycin Therapy Reduces Card
Page 27 and 28: 10 Evidence of Angiotensin II-depen
Page 29 and 30: 12 Auditory Entrainment of Respirat
Page 31 and 32: 14 Cardiac specific Rad knockout In
Page 33 and 34: 16 Hypercholesterolemia Induces Acu
Page 35 and 36: 18 A Novel Approach for Modifying I
Page 37 and 38: 20 Clinical Use of the Amplatzer Se
Page 39 and 40: 22 Regulation of Akt Signaling by N
Page 41 and 42: 24 Vascular Inflammatory Regulation
Page 43 and 44: 26 Vascular inflammation induced ex
Page 45 and 46: 28 Sexual Dimorphism of Angiotensin
Page 47 and 48: 30 Computational modeling of amylin
Page 49 and 50: 32 PCB 126 Exposure Increases Perip
Page 51: 34 Endothelial Mineralocorticoid Re
Page 55 and 56: 38 Gestational Diabetes Provokes Po
Page 57 and 58: 40 The Prognostic Role of Elevated
Page 59 and 60: 42 Lysophosphatidic Acid Receptor 4
Page 61 and 62: 44 Recapitulating In Vivo Fibroblas
Page 63 and 64: 46 Sex-Specific Differences in Card
Page 65 and 66: 48 Ticagrelor Reduces Inflammation
Page 67 and 68: 50 Association between Plasma Chole
Page 69 and 70: 52 Does Light Pollution Affect the
Page 71 and 72: 54 Impact of miR-33 antagonism on m
Page 73 and 74: 56 Isolation and characterization o
Page 75 and 76: 58 The XY sex chromosome complement
Page 77 and 78: 60 CHROME: a Long Non-coding RNA th
Page 79 and 80: 62 Making Good: Secretory Quality C
Page 81 and 82: 64 Thrombospondin 1 (TSP1) Deficien
Page 83 and 84: 66 Serum Amyloid A3 is a High Densi
Page 85 and 86: 68 Adipocyte deficiency of ACE2 inc
Page 87 and 88: 70 Hypercholesterolemia-induced end
Page 89 and 90: 72 Increased Circulating Trimethyla
Page 91 and 92: 74 Circulating Bacterial Small RNA
Page 93 and 94: 76 Pancreatic Beta Cell Export of m
Page 95 and 96: 78 Understanding inhibition of lipo
Page 97 and 98: 80 Insulin signaling regulates apol
Page 99 and 100: 82 Protease-activated Receptor 2 De
Page 101 and 102: 84 Reduced Low-Density Lipoprotein
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86 Pharmacological inhibition of Hu
Page 105 and 106:
88 The Effects of Hypercholesterole
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90 Reduced HDL in mice overexpressi
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92 Human Antigen R (HuR) Regulates
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94 Impact of miR-33 antagonism on c
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96 HB-EGF is a Key Positive Regulat
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98 HDL-miR-223 Communication Pathwa
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100 Short-Term Exercise Training Di
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102 The Ral-Exocyst Pathway Regulat
Page 121 and 122:
NOTES 120
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