Role of vascular endothelial growth factor B in the cardiovascular complications of diabetes
department or school: Pharmaceutical Sciences, Faculty of
data provider: DSpace
degree campus: UBCV
creator: Wang, Hualin
issued: 2024-10-09T08:09:01Z
issued: 2024
related degree: Master of Science - MSc
degree grantor: University of British Columbia
description: Diabetes affects over half a billion people worldwide, with cardiovascular disease (CVD) as the leading cause of death among diabetes patients. Heart failure can result from diabetic cardiomyopathy (DCM). Altered cardiac metabolism contributes significantly to the development of DCM via augmenting fatty acid (FA) delivery and metabolism in the heart, resulting in oxidative stress and lipid accumulation in the heart. Inhibition of vascular endothelial growth factor B (VEGFB) has been reported to counter these factors associated with abnormal cardiac metabolism by inducing metabolic flexibility and preventing FA flux to the heart. In this study, the role of VEGFB in diabetes has been investigated as a potential therapy for DCM. Knockout (KO) of VEGFB globally in rats had subtle phenotype and transcriptome changes under normal conditions including decreased white adipose tissue (WAT) lipolysis, and decreased cardiac lipoprotein lipase (LPL) activity probably by hindering LPL translocation from cardiomyocyte (CMO) to coronary vasculature. With the induction of diabetes with streptozotocin (STZ), VEGFB KO rats displayed increased cardiac LPL activity compared to wildtype (WT) rats. This increase in LPL activity prevented animals from dyslipidemia and provided more LPL-derived FA, which inhibited excess FA oxidation, sustained angiogenesis and alleviated cell death in the heart. Inhibiting VEGFB could be a promising therapeutic strategy to address the current lack of mechanism-based treatments for DCM. Future studies on cardiomyocytes are anticipated to further explore the signaling pathways involved in VEGFB's regulation of LPL translocation, which will be crucial for advancing drug development.
aggregated CHO: https://circle.library.ubc.ca/rest/handle/2429/89357
note: Role of Vascular Endothelial Growth Factor B in the Cardiovascular Complications of Diabetes by Hualin Wang B.Sc., University of Toronto, 2022 A THESIS SUBMITTED IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE DEGREE OF MASTER OF SCIENCE in THE FACULTY OF GRADUATE AND POSTDOCTORAL STUDIES (Pharmaceutical Sciences) THE UNIVERSITY OF BRITISH COLUMBIA (Vancouver) October 2024 © Hualin Wang, 2024 ii The following individuals certify that they have read, and recommend to the Faculty of Graduate and Postdoctoral Studies for acceptance, the thesis entitled: Role of Vascular Endothelial Growth Factor B in the Cardiovascular Complications of Diabetes submitted by Hualin Wang in partial fulfilment of the requirements for the degree of Master of Science in Pharmaceutical Sciences Examining Committee: Dr. Brian Rodrigues, Professor, Pharmaceutical Sciences, UBC Supervisor Dr. Colin Ross, Professor, Pharmaceutical Sciences, UBC Supervisory Committee Member Dr. Nicole Krentz, Assistant Professor, Pharmaceutical Sciences, UBC Supervisory Committee Member Dr. Thomas Pulinilkunnil, Professor, Department of biochemistry and molecular biology, Dalhousie University Supervisory Committee Member Dr. Ying Wang, Assistant Professor, Department of Pathology and Laboratory Medicine, Faculty of Medicine, UBC Additional Examiner iii Abstract Diabetes affects over half a billion people worldwide, with cardiovascular disease (CVD) as the leading cause of death among diabetes patients. Heart failure can result from diabetic cardiomyopathy (DCM). Altered cardiac metabolism contributes significantly to the development of DCM via augmenting fatty acid (FA) delivery and metabolism in the heart, resulting in oxidative stress and lipid accumulation in the heart. Inhibition of vascular endothelial growth factor B (VEGFB) has been reported to counter these factors associated with abnormal cardiac metabolism by inducing metabolic flexibility and preventing FA flux to the heart. In this study, the role …
has type: Thesis/Dissertation
date issued: 2024-11
is shown at: 10.14288/1.0445515
language: eng
degree discipline: Pharmaceutical Sciences
provider: Vancouver : University of British Columbia Library
publisher: University of British Columbia
rights: Attribution-NonCommercial-NoDerivatives 4.0 International
rights URI: http://creativecommons.org/licenses/by-nc-nd/4.0/
scholar level: Graduate
contributor: Rodrigues, Brian
type: Text
identifier URI: http://hdl.handle.net/2429/89357