Dietary polyphenols and cardiovascular diseases: investigation of novel biological activities relating to vascular function

Rujia Jiang

    Research output: ThesisDoctoral Thesis

    134 Downloads (Pure)

    Abstract

    [Truncated] Cardiovascular disease (CVD) is the major cause of mortality worldwide. As indicated by epidemiological studies, regular dietary intake of plant-derived foods and beverages benefits cardiovascular health and reduces the risk of CVD. Many studies have suggested that the polyphenol components in these diets are the main contributors towards improved cardiovascular health. Chlorogenic acid (CGA) is the major polyphenol found in coffee, accounting for almost 86% of total polyphenol content. Whilst the beneficial effects of other polyphenols such as quercetin, a major polyphenol found in a wide range of fruits and vegetables, on cardiovascular health have been shown, considerably less is known of the effects of CGA. Structural modification of polyphenols by metabolic transformation in the gut is likely to have a profound effect on biological activity. However, studies towards this area are still very limited.

    Endothelial dysfunction is an early and major risk factor for CVD, with nitric oxide (NO) being a key regulator of endothelial function. Oxidative stress plays a critical role in the development of endothelial dysfunction. Heme oxygenase-1 (Hmox-1) is an inducible isoform of heme oxygenase that is produced in response to stressors such as oxidative stress, and may play a role in vascular protection. The aim of our first study was to investigate the effect of CGA on endothelial function with oxidant-induced damage in isolated aortic rings from wild-type mice. I further examine the mechanism by investigating cell viability, activation of eNOS and induction of Hmox-1 in human aortic endothelial cells (HAECs). I found that pre-treatment of isolated aortic rings with 10μM CGA protected vessels against HOCl-induced endothelial dysfunction (P<0.05). Pre-treatment of cultured HAECs with 10μM CGA also increased endothelial cell viability following exposure to HOCl (P<0.05). In addition, CGA increased NO production in HAECs in a dose-dependent manner, peaking at 6h (P<0.05). 5μM and 10μM CGA also increased eNOS dimerization at 6h and induced Hmox-1 protein expression at 6h and 24h in HAECs. These results are consistent with the cardiovascular protective effects of coffee polyphenols and demonstrate that CGA can protect vessels and cultured endothelial cells against oxidant-induced damage. The mechanism behind the beneficial effect of CGA appears to be in part via increased production of NO and induction of Hmox-1.

    Original languageEnglish
    QualificationDoctor of Philosophy
    Supervisors/Advisors
    • Hodgson, Jonathan, Supervisor
    • Ward, Natalie, Supervisor
    • Croft, Kevin, Supervisor
    Publication statusUnpublished - 2015

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