Studies on the anti-atherogenic and anti-steatotic actions of (+) catechin

Alshehri, Nouf 2024. Studies on the anti-atherogenic and anti-steatotic actions of (+) catechin. PhD Thesis, Cardiff University. Item availability restricted.

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Abstract

Background: Atherosclerosis is a persistent inflammatory condition marked by the buildup of lipids in the walls of arteries. It is widely recognised as a significant factor in the development of cardiovascular disease (CVD). Current pharmacological interventions aimed at treating hyperlipidaemia, such as statins, are associated with considerable residual risk for CVD together with various side effects. Consequently, there is an need for alternative medications to prevent and cure the condition. Previous studies in the host laboratory found (+) Catechin to exert various anti-inflammatory and anti-atherogenic effects on different types of cells in vitro and in male LDL receptor-deficient mice (LDLr-/-) fed a high-fat diet (HFD) in vivo. This study focused on investigation of the effects of (+) Catechin on atherosclerosis development and progression in female LDLr-/- mice together with the underlying molecular mechanisms given the existence of sex-specific differences in nutraceutical actions, and to attenuate parameters associated with smooth muscle cells (SMC) dysfunction. Methods: In order to study the development of atherosclerosis in vivo, 8-week-old female LDLr-/- mice were fed HFD either alone or supplemented with 200 mg/kg/day of (+) Catechin for 12 weeks. Subsequently, a thorough examination of the risk factors linked with atherosclerosis together with plaque parameters in the aortic root were carried out. The liver was also examined in relation to non-alcoholic fatty liver disease (NAFLD), which is frequently linked to atherosclerosis. RNA-sequencing was also utilised to evaluate alterations in gene expression in the thoracic aorta and liver tissue. In vitro, multiple assays were employed to replicate SMC dysfunction using human aortic smooth muscle cells (HASMCs), allowing for the investigation of the molecular mechanisms via which (+) Catechin improves plaque stability. Results: Female LDLr-/- mice that were given a HFD supplemented with (+) Catechin for a duration of 12 weeks showed an improvement in their plasma lipid profile, a reduction in inflammation of the plaque and an increase in the stability of the plaque. Moreover, further examination of liver samples and in vitro model of NAFLD revealed that (+) Catechin has the capacity to decrease steatosis. In addition, (+) Catechin reduces the formation of SMC foam cells, which may play a role in its ability to improve the development of atherosclerosis in LDL-/- mice. Conclusions: The results of this study offer significant insights about the anti-atherogenic effects of (+) Catechin and suggest that it could be a promising nutraceutical candidate for preventing and managing atherosclerotic CVD worldwide. This is possibly achievable because of its lack of adverse side effects and the comparatively affordable price compared to conventional pharmaceutical therapies. Further exploration of the potential of (+) Catechin should be conducted through extensive clinical trials.

Item Type:	Thesis (PhD)
Date Type:	Completion
Status:	Unpublished
Schools:	Biosciences
Subjects:	Q Science > Q Science (General)
Date of First Compliant Deposit:	30 January 2025
Last Modified:	30 Jan 2025 15:03
URI:	https://orca.cardiff.ac.uk/id/eprint/175765

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