Vascular endothelial growth factor B and its action in the diabetic heart
department or school: Pharmaceutical Sciences, Faculty of
data provider: DSpace
degree campus: UBCV
creator: Lal, Nathaniel
issued: 2022-06-30T07:00:00Z
issued: 2020
related degree: Doctor of Philosophy - PhD
degree grantor: University of British Columbia
description: Fatty acid (FA) provision to the heart is from cardiomyocyte and adipose depots, plus lipoprotein lipase (LPL) action. Changes in cardiac metabolism (reduced glucose, greater FA utilization) is a major contributor towards diabetic cardiomyopathy. Vascular endothelial growth factor B (VEGFB) can regulate coronary angiogenesis and influence energy metabolism. Multiple models of heart failure have indicated a significant drop in VEGFB. In this thesis we hypothesized that there is a role for VEGFB in diabetic cardiomyopathy. The objectives of this thesis were to: Determine the changes in cardiac metabolism following diabetes with its effect on VEGFB production. Investigate the mechanisms behind VEGFB action in the heart subsequent to diabetes. Identify the potential benefits of VEGFB following chronic diabetes. With increasing severity of diabetes and dramatic loss of insulin, the heart is unable to control its own FA supply using LPL and undergoes dramatic reprogramming that is linked to handling of excess FA that arise from adipose tissue. This transition results in a cardiac metabolic signature that exhibits mitochondrial FA overload, oxidative stress, triglyceride storage and cell death. Under these conditions VEGFB production is impaired. Mechanistically, the immediate response to high glucose and the secretion of endothelial heparanase is the release of cardiomyocyte surface bound VEGFB, which triggers signaling pathways and gene expression to influence cardiomyocyte (autocrine action) and endothelial cell (paracrine effects) survival. Defects in numerous VEGFB pathways were associated with an increased cell death signature in our models of diabetes. Overexpression of VEGFB in the heart can regulate coronary angiogenesis and influence energy metabolism and we tested whether these effects can overcome the detrimental consequences of diabetes. VEGFB overexpression induced an angiogenic response that resulted in greater delivery of insulin, amplifying its action in t…
aggregated CHO: https://circle.library.ubc.ca/rest/handle/2429/74840
note: VASCULAR ENDOTHELIAL GROWTH FACTOR B AND ITS ACTION IN THE DIABETIC HEART by Nathaniel Lal A THESIS SUBMITTED IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE DEGREE OF Doctor of Philosophy in THE FACULTY OF GRADUATE AND POSTDOCTORAL STUDIES (Pharmaceutical Sciences) THE UNIVERSITY OF BRITISH COLUMBIA (Vancouver) July 2020 © Nathaniel Lal, 2020 The following individuals certify that they have read, and recommend to the Faculty of Graduate and Postdoctoral Studies for acceptance, the dissertation entitled: Vascular endothelial growth factor b and its action in the diabetic heart submitted by Nathaniel Lal in partial fulfillment of the requirements for the degree of Doctor of Philosophy in Pharmaceutical Sciences Examining Committee: Dr. Brian Rodrigues, Pharmaceutical Sciences Supervisor Dr. Judy Wong, Pharmaceutical Sciences Supervisory Committee Member Dr. Colin Ross, Pharmaceutical Sciences University Examiner Dr. Pascal Bernatchez, Medicine University Examiner Additional Supervisory Committee Members: Dr. Angela Devlin, Medicine Supervisory Committee Member Dr. Susanne Clee, Medicine Supervisory Committee Member i ABSTRACT Fatty acid (FA) provision to the heart is from cardiomyocyte and adipose depots, plus lipoprotein lipase (LPL) action. Changes in cardiac metabolism (reduced glucose, greater FA utilization) is a major contributor towards diabetic cardiomyopathy. Vascular endothelial growth factor B (VEGFB) can regulate coronary angiogenesis and influence energy metabolism. Multiple models of heart failure have indicated a significant drop in VEGFB. In this thesis we hypothesized that there is a role for VEGFB in diabetic cardiomyopathy. The objectives of this thesis were to: Determine the changes in cardiac metabolism following diabetes with its effect on VEGFB production. Investigate the mechanisms behind VEGFB action in the heart subsequent to diabetes. Identify the potential benefits of VEGFB following chronic diabetes. With increasing severity of diabet…
has type: Thesis/Dissertation
date issued: 2020-11
is shown at: 10.14288/1.0392046
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
type: Text
identifier URI: http://hdl.handle.net/2429/74840