Investigating mitochondrial impairment as a mechanism of statin-induced muscle toxicity



Jones, SW
(2019) Investigating mitochondrial impairment as a mechanism of statin-induced muscle toxicity. Doctor of Philosophy thesis, University of Liverpool.

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Abstract

Statins, also known as 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-CoAR) inhibitors, are currently the pharmaceutical intervention strategy of choice for the primary and secondary prevention of atherosclerotic disorders that are related to hypercholesterolemia. In most recipients, statin therapy is effective and well tolerated, however the most significant barrier to cardiovascular disease (CVD) risk reduction is the development of adverse effects, of which statin-related myopathies (SRM) are the most frequently reported. The aetiological basis of SRM is both complex and multifaceted, with no clear dose-response relationship and a plethora of generalised and genetic risk factors identified to date. However, the deleterious effects of statins upon mitochondrial function has been implicated as one of several putative mechanisms by which myopathic symptoms may be potentiated in some patients. Therefore, the aim of this research was to establish the effects of statin chemical species (i.e. inactive lactones versus active ß-hydroxy acids) upon the functionality of the mitochondrial electron transport chain using high resolution respirometry. Thereafter, the remainder of the thesis focussed upon the development ... (continues)

Item Type: Thesis (Doctor of Philosophy)
Divisions: Faculty of Health and Life Sciences > Institute of Life Courses and Medical Sciences > School of Medicine
Depositing User: Symplectic Admin
Date Deposited: 06 Jan 2020 10:47
Last Modified: 07 Feb 2025 13:30
DOI: 10.17638/03055069
Supervisors:
URI: https://livrepository.liverpool.ac.uk/id/eprint/3055069