2017 Cardiovascular Research Day Abstract Book

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101 Identification of a novel lipoprotein microRNA carrier in plasma Wanying Zhu 1 • Danielle L. Michell 1 • Ryan M. Allen 1 • Kasey C. Vickers 1 Vanderbilt University Medical Staff Recently, multiple groups have detected of microRNAs (miRNA) in plasma by high-throughput sequencing. Circulating sRNAs are likely protected from RNases in plasma through their association with lipid carriers. Our lab previously reported that lipoproteins (HDL and LDL) transport miRNAs in plasma within potential intercellular communication networks. Based on these previous studies, we sought to define the distribution of miRNAs across lipid carriers in plasma. Methods: To specifically precipitate carriers, whole plasma and pre-purified HDL (density-gradient ultracentrifugation) treated with lipid removal agents (LRA and Cleanascite) for the separation of lipid-associated miRNAs. Plasma samples from humans and mice were fractionated using sizeexclusion chromatography (FPLC, Superdex 200 Increase in triplicate). Each fraction was assessed for total cholesterol, triglycerides, protein, phospholipids, and markers for lipoproteins and extracellular vesicles by western blotting. Carrier sizes in each fraction were quantified using dynamic light scattering. Total RNA was isolated from whole fractions and separated contents, lipid pellets and supernatants, after centrifugation. Real-time PCR and high-throughput sequencing were used to quantify miRNAs. Results: Results demonstrated that Cleanascite efficiently removed lipids from plasma without damaging lipoproteins, as determined by the lack of phospholipids and apolipoproteins in the supernatants. Candidate miRNAs (miR-24-3p, miR-26a-5p, miR-146a-5p, miR-92a-3p, and miR- 223-3p) were detected in fractions corresponding to HDL and LDL based on the distribution of cholesterol and triglycerides. Strikingly, candidate miRNAs also entirely separated with lipids in fractions that contained low cholesterol and high phospholipid content with a mass corresponding to very small HDL. These fractions were found to contain apoA-I and spherical particles
102 The Ral-Exocyst Pathway Regulates Platelet Secretion Jinchao Zhang 1 and Sidney W. Whiteheart 1 1 Department of Molecular and Cellular Biochemistry, College of Medicine, University of Kentucky Postdoc In Platelets, Exocyst complex has been identified as an octamer consisting of Sec3, Sec5, Sec6, Sec8, Sec10, Sec 15, Exo70 and Exo84 in platelets. The complex plays an essential role in tethering vesicles to the plasma membrane and regulating dense core granule secretion in platelets. RalA/B (family members of GTPases) are regarded as the upstream regulator of the Exocyst complex, and RalA/B binds to Sec5 and Exo84 in a GTP-dependent manner. RalA/B, sharing over 88% identity in sequences, directly interact with Exo84 and Sec5 in the Exocyst complex. The role of RalA/B are interchangeable, but RalA has the higher ability to bind to the Exocyst components in GTP binding manner in cells. Several groups suggest that interrupting the association Sec3 and Exo70 with plasma membrane could disrupt exocytosis in other cells. However, it is little known how the role of the Exocyst complex in platelet secretion. Here we ask the question whether inhibitors of RalA/B could affect granule secretion or not in platelets. And what is the exact role of the Exocyst complex in granule secretion? How is the Exocyst complex regulating vesicles tethering in secretion process? Firstly, specific RalA/B inhibitors, RBC8 and BQU57, were used to investigate the role of RalA/B in granule secretions. From the biochemical perspective, these inhibitors affect RalA/B bound to their downstream effector (RLP76) due to the Ral-GDP bound forms. We also found the inhibitors of RalA/B affects platelet spreading (data are not shown here). At the same time, we also answer the questions of the localization of Rals and Exo70 (one of the Exocyst component) as well as their association with F-actin. 118
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Cardiovascular Research Day ABSTRAC
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SCHEDULE FOR THE DAY Friday, Novemb
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SCHEDULE FOR THE DAY continued Frid
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2017 GILL HEART INSTITUTE YOUNG INV
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FEATURED SPEAKER Calum MacRae, M.D.
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SPECIAL PRESENTATION Mark Stoops He
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NOTES 12
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2017 POSTER PARTICIPANTS 40 Mohamed
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2017 ABSTRACTS 16
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2 Inhibition of Megalin Reduces Ath
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4 Identification of a Lipid Signatu
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6 Serum Amyloid A Activates the NLR
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8 Azithromycin Therapy Reduces Card
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10 Evidence of Angiotensin II-depen
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12 Auditory Entrainment of Respirat
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14 Cardiac specific Rad knockout In
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16 Hypercholesterolemia Induces Acu
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18 A Novel Approach for Modifying I
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20 Clinical Use of the Amplatzer Se
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22 Regulation of Akt Signaling by N
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24 Vascular Inflammatory Regulation
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26 Vascular inflammation induced ex
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28 Sexual Dimorphism of Angiotensin
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30 Computational modeling of amylin
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32 PCB 126 Exposure Increases Perip
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34 Endothelial Mineralocorticoid Re
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36 Optimization of immunomagnetic s
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38 Gestational Diabetes Provokes Po
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40 The Prognostic Role of Elevated
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42 Lysophosphatidic Acid Receptor 4
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44 Recapitulating In Vivo Fibroblas
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46 Sex-Specific Differences in Card
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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
Page 103 and 104: 86 Pharmacological inhibition of Hu
Page 105 and 106: 88 The Effects of Hypercholesterole
Page 107 and 108: 90 Reduced HDL in mice overexpressi
Page 109 and 110: 92 Human Antigen R (HuR) Regulates
Page 111 and 112: 94 Impact of miR-33 antagonism on c
Page 113 and 114: 96 HB-EGF is a Key Positive Regulat
Page 115 and 116: 98 HDL-miR-223 Communication Pathwa
Page 117: 100 Short-Term Exercise Training Di
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2017 Cardiovascular Research Day Abstract Book

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