Physiological aspects of iron status and manipulation in lowlander and adapted highlanders at high altitude
department or school: Health and Social Development, Faculty of (Okanagan)
department or school: Health and Exercise Sciences, School of (Okanagan)
data provider: DSpace
degree campus: UBCO
creator: Patrician, Alexander M. D.
issued: 2022-04-06T15:42:36Z
issued: 2022
related degree: Doctor of Philosophy - PhD
degree grantor: University of British Columbia
description: With ascent to high altitude, the reduction in the partial pressure of oxygen (PO₂) drives the stabilization of the hypoxia-inducible factor (HIF) family. As the key cellular oxygen sensor, HIF up-regulates the expression of numerous genes designed to increase and preserve O₂ tissue delivery. Since iron plays an inverse and constituent role in HIF stabilization, the overall objectives of the current thesis were: 1) determine the role of iron status manipulation on pulmonary, peripheral and cerebral responses to high-altitude; 2) and examine if indigenous high-altitude populations (i.e. Sherpa and Andeans), with ancestral adaptation to their hypoxic environment, exhibit iron-regulatory advantages. Study 1 investigated the effects of ascent and prolonged stay at 5050 m on iron status and hypoxic pulmonary vasoconstriction. The primary findings were that 1) during ascent, reductions in iron bioavailability were more prevalent in lowlanders, compared to Sherpa; 2) following partial acclimatization to 5050 m, iron infusion (HIF-down regulation) attenuated pulmonary artery systolic pressure (PASP) in both lowlanders and Sherpa while deferoxamine infusion (HIF-up regulation) had little influence. Study 2, in a block-randomized and placebo-controlled design, examined whether the pulmonary vasculature of lowlanders and adapted Andeans at 4300 m are responsive to iron infusion. The findings revealed that, unlike the placebo condition, iron infusion reduced PASP in both lowlanders and Andeans. Study 3 then evaluated the role of iron infusion on peripheral vascular function in the same volunteers at 4300 m. Here, iron infusion (but not saline) increased brachial blood flow and increased microvascular function across the 4-hours, in both lowlanders and Andeans. Upon pooling data (n=83), across both lowlanders and highlanders, Study 4 explored whether the same iron manipulations can modulate hypoxic cerebral vasodilation. It was found that baseline iron levels were related to the…
aggregated CHO: https://circle.library.ubc.ca/rest/handle/2429/81101
note: i Physiological aspects of iron status and manipulation in lowlander and adapted highlanders at high altitude by Alexander M. D. Patrician M.Sc, Mid Sweden University 2015 A THESIS SUBMITTED IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE DEGREE OF Doctorate of Philosophy In THE COLLEGE OF GRADUATE STUDIES (Interdisciplinary Studies) (Health and Exercise Sciences) THE UNIVERSITY OF BRITISH COLUMBIA (Okanagan) March 2022 © Alexander M. D. Patrician, 2022 ii The following individuals certify that they have read, and recommend to the College of Graduate Studies for acceptance, a thesis/dissertation entitled: Physiological aspects of iron status and manipulation in lowlander and adapted highlanders at high altitude submitted by Alexander M. D. Patrician in partial fulfillment of the requirements of the degree of Doctorate of Philosophy. Prof. Philip Ainslie, School of Health & Exercise Sciences Supervisor Prof. Neil Eves, School of Health & Exercise Sciences Supervisory Committee Member Prof. Jonathan Little, School of Health & Exercise Sciences Supervisory Committee Member Prof. William Sheel, School of Kinesiology University Examiner Dr. Nisha Charkoudian, United States Army Research Institute of Environmental Medicine External Examiner iii Abstract With ascent to high altitude, the reduction in the partial pressure of oxygen (PO2) drives the stabilization of the hypoxia-inducible factor (HIF) family. As the key cellular oxygen sensor, HIF up-regulates the expression of numerous genes designed to increase and preserve O2 tissue delivery. Since iron plays an inverse and constituent role in HIF stabilization, the overall objectives of the current thesis were: 1) determine the role of iron status manipulation on pulmonary, peripheral and cerebral responses to high-altitude; 2) and examine if indigenous high-altitude populations (i.e. Sherpa and Andeans), with ancestral adaptation to their hypoxic environment, exhibit iron-regulatory advantages. Study 1 investigated th…
has type: Thesis/Dissertation
date issued: 2022-05
is shown at: 10.14288/1.0412620
language: eng
degree discipline: Interdisciplinary Studies
provider: Vancouver : University of British Columbia Library
publisher: University of British Columbia
rights: Attribution-NonCommercial-ShareAlike 4.0 International
rights URI: http://creativecommons.org/licenses/by-nc-sa/4.0/
scholar level: Graduate
contributor: Ainslie, Philip N., 1974-
type: Text
identifier URI: http://hdl.handle.net/2429/81101