Views
4 months ago

2017 Cardiovascular Research Day Abstract Book

41 Desynchrony of Tissue

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

Book of Abstracts - Australian Centre for Economic Research on ...
Abstract Book Research Day 2013.pdf - University of Minnesota ...
Research Day Book 2013 - College of Medicine - Florida Atlantic ...
Abstract Book - Pathology and Laboratory Medicine - University of ...
Assessment of Tobacco Smoke-Mediated Atherosclerosis in Mouse ...
Research Days 2013 Abstract Book - Office of the Vice President for ...
2010 Abstracts - Radiation Research Society
Abstract Booklet - University of Ottawa Heart Institute
book of abstracts 11th annual research half day may 12, 2010 ...
research day - University of Toronto Department of Obstetrics and ...
Abstracts - Society of Cardiovascular Anesthesiologists
Abstracts - Interactive CardioVascular and Thoracic Surgery
Abstracts for The European Society for Cardiovascular Surgery 53rd ...
CARDIOVASCULAR DISEASE IN WOMEN - Epib.nl
Conditional Risk Factors for Atherosclerosis - Mayo Medical ...
Reverse cholesterol transport and cholesterol efflux in atherosclerosis
The interplay of inflammation and cardiovascular disease in ...
Oral Presentations - Arteriosclerosis, Thrombosis, and Vascular ...
PATHOLOGY OF THE CARDIOVASCULAR SYSTEM Dr: Khitam Dr ...
Book of Abstracts - Oxygen Club of California
Research Days Abstract Book - Office of the Vice President for ...
Oral Abstracts - Society of Cardiovascular Magnetic Resonance
Technologist Abstracts - Society of Cardiovascular Magnetic ...
Cardiovascular Pharmacology - Icuadelaide.com.au
Oral Abstracts - Society of Cardiovascular Magnetic Resonance