Year

2021

Degree Name

Doctor of Philosophy

Department

School of Medicine

Abstract

Vascular health plays a major role in several human disorders, particularly in cardiovascular diseases (CVD) (1,2). The endothelium can be considered an organ that regulates vascular homeostasis by maintaining an appropriate vascular tone, platelet activity, leukocyte adhesion and angiogenesis. When one or more of these components is compromised due to impaired endothelial vascular signalling, endothelial dysfunction (ED) may occur (1). One of the main key metabolic manifestations of ED is reduced nitric oxide (NO) bioavailability. NO is an important signalling molecule that regulates various vascular processes, including through its main role as a vasodilator, acting through relaxation of smooth muscle cells (2,3). Impaired bioavailability of NO and up-regulation of various molecules involved in vascular function are partly explained by the cooperative and synergistic action of inflammation and oxidative stress on ED (4–6). This is particularly evident in older adults, as several studies support a new immune-metabolic viewpoint for age-related diseases, termed “inflammaging” which is characterized by a chronic low-grade inflammation (7). Thus, interventions aiming to regulate the immune response and to prevent the accumulation of deleterious reactive species, have been considered to be a relevant therapeutic target to improve vascular health (8).

Nutrition plays a major role in regulating the inflammatory state and enhancing endogenous antioxidant defences (9). Many dietary patterns have been associated with the prevention of diseases associated with inflammation in epidemiological studies (10), while at the same time a large range of dietary interventions have been explored in clinical practice to treat pathological conditions such as ED (11). Flavonoids, a class of dietary polyphenols, are bioactive compounds that have potential to both prevent and treat conditions related to a pro- inflammatory and oxidative stress state (12,13). Meta-analysis of controlled trials and cohort 3 studies demonstrate a protective effect of flavonoid intake on CVD (14–18), particularly on hypertension (19,20). Anthocyanins, a subclass of flavonoids, are emerging as a potential therapeutic option for CVD risk factors (21). Anthocyanins are the largest class of water- soluble plant pigments, that are responsible for the blue, purple and red colour of many fruits and vegetables, such as blueberries, blackberries, red grapes, plums and eggplants (22). The beneficial effects of anthocyanins on CVD risk factors are related to their antioxidant and immunomodulatory effects, thereby attenuating the synergistic deleterious effects of oxidative stress and inflammation in CVD (21,23). In humans, anthocyanin intake has been shown to be associated with a lower risk of cardiovascular events (24,25). Intervention studies using anthocyanins have demonstrated improvements in vascular function (26) and biomarkers related to oxidative stress (27–30), as well as antioxidant status (28,30–32), lipid profile (33– 35) and inflammatory response (36,37) in both long-term and acute designs.

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Unless otherwise indicated, the views expressed in this thesis are those of the author and do not necessarily represent the views of the University of Wollongong.