2017 Cardiovascular Research Day Abstract Book

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41 Desynchrony of Tissue Oscillators and Compromised Blood Pressure Circadian Rhythm in a Novel Diabetic Db/Db-Mper2luc Mouse Model Tianfei Hou, MS 1 • Wen Su, MD 1 • Ming Gong, MD, PhD 2 • Zhenheng Guo, PhD 1 1Department of Pharmacology and Nutritional Sciences, University of Kentucky • 2 Department of Physiology, University of Kentucky Graduate Student Diabetic patients have a high prevalence of blood pressure (BP) circadian rhythm disruption mostly manifested as reduced BP dipping during the inactive phase (non-dipping profile). Accumulating evidence demonstrates a pathophysiological link between end-organ damage and non-dipping BP. Clock gene dysregulation may link diabetes with non-dipping BP but comprehensive study of clock gene oscillation dysregulation in diabetes has been hampered by the impractical requirement of intensive timed sampling. To address this issue, we generated a novel diabetic model, db/dbmPer2Luc mouse, by crossing the extensively used type 2 diabetic db/db mice with the clock gene Period 2 (mPer2) luciferase knock-in mPer2Luc mice. The db/db-mPer2Luc mice were obese, diabetic and had non-dipping BP. Real-time measurement of bioluminescence of the many tissues explanted from the db/db-mPer2Luc mice revealed that the phases of the mPer2 circadian oscillations shifted to different extents in aorta, mesenteric artery, kidney, liver, white adipose tissue and thymus, but no phase shift was detected in the central SCN tissue, or the adrenal gland and lung. The desynchrony of the tissue oscillators in the db/db-mPer2Luc mice was associated with compromised circadian rhythms in respiratory exchange ratio. Moreover, the time-of-day variations in vascular contractile responses and in baroreflex sensitivity were abolished. Taken together, we generated a novel diabetic db/db-mPer2Luc mouse model. Using this model, we revealed a desynchrony among tissue oscillators, a loss of the time-of-day variations in vascular contractile responses and baroreflex sensitivities, all of which likely contribute to the dampening of BP circadian rhythm in diabetes. 57
42 Lysophosphatidic Acid Receptor 4 Influence The development of Atherosclerotic Vascular Disease in Mouse Model Liping Yang, MD 1 • Andrew Morris, PhD 1 • Susan Smyth, MD, PhD 1 1Internal Medicine - Cardiology, University of Kentucky Staff Background: Lysophosphatidic acid (LPA) is one of the simplest phospholipid signaling molecules. LPA elicits diverse biological functions including cell proliferation, differentiation, migration, survival and apoptosis through binding and activating specific cell surface G-protein coupled receptors (LPA1-6). LPA1/Edg2, LPA2/Edg4 and LPA3/Edg7 receptors are the endothelial differentiation gene (Edg) family. LPA4/p2y9/GPR23 of the purinergic receptor family and the related LPA5/GPR92 and LPA6/p2y5 have been identified as novel LPA receptors. LPA is generated by the secreted lysophospholipase D autotaxin (ATX) and inactivated by dephosphorylation by membrane lipid phosphate phosphatases (LPPs). Our previous work established that ATX and LPP3 contribute to atherosclerotic vascular disease, but little is known about the role of specific LPA4 receptors in atherosclerosis. We recently demonstrated upregulation of LPA4 in SMC undergoing a switch to assume a foam-cell like phenotype. The present work therefore aims to elucidate an association between LPA4 and experimental atherosclerosis in mice. Methods and Results: We generated mouse globally lacking LPA4 (LPA4-/-) on C57/BL background. Hyperlipidemia was elicited in the mice by PCSK9 virus injection at 5 weeks of age and then Western Diet feeding for 20 weeks. Although plasma cholesterol levels were similar, en face analysis of aortic atherosclerosis indicated a significant reduction in plaque area in LPA4-/- compared to LPA4-WT mice. Oil Red-O staining of aortic roots confirmed reduced neutral fat accumulation in the aortic roots of LPA4-/-mice. In sections taken at the level of the aortic root, CD68 and α-SMA immunoreactivity was lower in the absence of LPA4. SMCs isolated from mouse thoracic aorta were treated with ox-LDL to promote a foam cell phenotype, characterized by upregulation of CD68 expression. SMC isolated from LPA4-/- mice had lower CD68 mRNA after ox- LDL exposure than LPA4-WT cells. Conclusion: These findings revealed a role for LPA4 in vascular inflammation and the development of atherosclerotic vascular disease, potentially through effects of SMC phenotype and function. 58
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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
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 and 52: 34 Endothelial Mineralocorticoid Re
Page 53 and 54: 36 Optimization of immunomagnetic s
Page 55 and 56: 38 Gestational Diabetes Provokes Po
Page 57: 40 The Prognostic Role of Elevated
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
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
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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
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NOTES 120
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2017 Cardiovascular Research Day Abstract Book

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