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Anti-atherogenic actions of (+)-catechin

Chan, Yee 2021. Anti-atherogenic actions of (+)-catechin. PhD Thesis, Cardiff University.
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Abstract

Introduction: Cardiovascular disease arising from atherosclerosis persists as a major cause of global morbidity and mortality. Pharmacological therapies targeted to lipid management, such as statins, can be effective but have various limitations hence alternative avenues are required. Previous studies conducted in the host laboratory found (+)-catechin (an understudied flavanol) to exert various anti-inflammatory and anti-atherogenic effects on human monocytes/macrophages, and modulated several atherosclerosis risk factors in wild-type mice fed a high-fat diet (HFD) for 3 weeks. The aims of this study were hence to determine whether (+)-catechin can attenuate parameters associated with endothelial and smooth muscle cell (SMC) dysfunction, and to elucidate its effects on atherosclerosis development and progression, and, regression, in a mouse model. Methods: Various in vitro assays were used to recapitulate endothelial and SMC dysfunction using human umbilical vein endothelial cells (HUVECs) and human aortic smooth muscle cells (HASMCs). Assays enabling the study of cellular bioenergetics and mitochondrial function were also used. In vivo, 8-week-old male low-density lipoprotein receptor-deficient (Ldlr-/-) mice were fed HFD alone or supplemented with (+)-catechin hydrate for 12 weeks to investigate atherosclerosis development and progression. For atherosclerosis regression, the same mice were fed HFD for 12 weeks to induce the formation of established lesions and then switched to chow alone or combined with (+)-catechin hydrate. Both protocols were followed up by detailed analyses of associated atherosclerosis risk factors and resulting atherosclerotic plaques in the aortic root. Results: As part of the key findings, (+)-catechin consistently attenuated reactive oxygen species production in all investigated cell types, stimulated HASMC migration, and demonstrated protective effects on mitochondrial function. As part of the progression study, Ldlr-/- mice that had received (+)-catechin supplemented HFD for 12 weeks had attenuated plaque burden and inflammation, and enhanced plaque stability. As part of the regression study, intervention with (+)-catechin combined with chow reversed adiposity and hepatic injury, whilst plaque stability was enhanced (to a greater extent than chow intervention alone). Conclusions: These data support the anti-atherogenic actions of (+)-catechin and its potential as an alternative preventative nutraceutical agent for atherosclerosis. Further studies are required to ascertain the mechanisms responsible for these beneficial observations in atherosclerosis development and progression. Future studies characterising the effect of (+)-catechin on atherosclerosis regression are also needed.

Item Type: Thesis (PhD)
Date Type: Completion
Status: Unpublished
Schools: Biosciences
Subjects: Q Science > Q Science (General)
Date of First Compliant Deposit: 20 October 2021
Last Modified: 20 Oct 2021 14:14
URI: https://orca.cardiff.ac.uk/id/eprint/144961

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