Vascular Function Prior to the Development of Overt Atherosclerosis

Abstract

Christopher John CobbUniversity of ManchesterDoctor of PhilosophyVascular function prior to the development of overt atherosclerosisSeptember 2013The formation of atherosclerotic plaques is linked to a change in vascular function, with evidence of endothelial dysfunction and the proliferation of the underlying vascular smooth muscle cells (VSMCs). Prior to plaque development, risk factors are present that are capable of altering vascular function and promoting disease progression. These risk factors include hypercholesterolaemia, obesity and inflammation. The specific mechanisms of these risk factors in the early stages of atherosclerotic disease development have yet to be fully explored and are likely to be closely interwoven. The aim of this thesis was to assess the effects of these atherosclerotic risk factors, with a primary focus on the direct action of hypercholesterolaemia, on vascular function prior to the development of overt atherosclerosis.After acute ex vivo cholesterol depletion and enrichment, a range of contractile and relaxant stimuli were applied to thoracic aortic rings of wildtype C57BL/6 mice. Cholesterol depletion significantly reduced contractility to phenylephrine (p

Date of Award	31 Dec 2013
Original language	English
Awarding Institution	The University of Manchester
Supervisor	Cathy Holt (Supervisor), Clare Austin (Supervisor) & David Eisner (Supervisor)