Functionality of HDL: Antioxidation and Detoxifying Effects
High-density lipoproteins (HDL) are complexes of multiple talents, some of which have only recently been recognised but all of which are under active investigation. Clinical interest initially arose from their amply demonstrated role in atherosclerotic disease with their consequent designation as a major cardiovascular disease (CVD) risk factor. However, interest is no longer conﬁned to vascular tissues, with the reports of impacts of the lipoprotein on pancreatic, renal and nervous tissues, amongst other possible targets. The ever-widening scope of HDL talents also encompasses environmental hazards, including infectious agents and environmental toxins. In almost all cases, HDL would appear to have a beneﬁcial impact on health. It raises the intriguing question of whether these various talents emanate from a basic ancestral function to protect the cell. The following chapter will illustrate and review our current understanding of some of the functions attributed to HDL. The ﬁrst section will look at the antioxidative functions of HDL and possible mechanisms that are involved. The second section will focus speciﬁcally on paraoxonase-1 (PON1), which appears to bridge the divide between the two HDL functions discussed herein.
This will lead into the ﬁnal section dealing with HDL as a detoxifying agent protecting against exposure to environmental pathogens and other toxins.
HDL • Lipoproteins • Oxidative stress • Paraoxonase • Organophosphates • Bacterial pathogen • Antiviral activity • Nanoparticles • Bisphenol
High-Density Lipoproteins and Oxidative Stress
The role of high-density lipoproteins (HDL) in the vascular system has been the primary focus of clinical interest. It arose from early studies of the inﬂuence of the lipoprotein on cholesterol metabolism and atherosclerosis. With increasing understanding of the complexity of the atherosclerotic process and involvement of other pathological mechanisms, attention has logically progressed to the impact of HDL on such mechanisms. One process is oxidative stress and there is now persuasive evidence that the lipoprotein can attenuate its consequences by a number of mechanisms. These are discussed in this section.
High-Density Lipoproteins: Antioxidative Function
The response-to-retention hypothesis of atherosclerosis (Williams and Tabas 1995) postulates that cholesterol-rich lipoproteins, primarily low-density lipoproteins (LDL), are retained in the arterial wall and oxidatively modiﬁed under the action of resident cells (Stocker and Keaney 2004). Oxidation in the arterial intima results from local oxidative stress, which represents an imbalance between prooxidants and antioxidants in favour of the former. Cellular oxidative systems involved in vivo include myeloperoxidase (MPO), NADPH oxidase, nitric oxide synthase and lipoxygenase. They produce a variety of reactive chlorine, nitrogen and oxygen species in the form of one-electron (free radical) and two-electron oxidants (Gaut and Heinecke 2001).
HDL can protect LDL and other lipoproteins from oxidative stress induced by both oneand two-electron species. It can be observed in vitro on their co-incubation (Parthasarathy et al. 1990) and in vivo upon HDL supplementation (Klimov et al. 1993). One-electron oxidants modify both lipid and protein moieties of HDL with formation of lipid and protein radicals. It is followed by accumulation of primary oxidation products, initially lipid hydroperoxides (LOOH), which in turn propagate further oxidation of HDL components to stable termination products (Stocker and Keaney 2004). HDL particles potently protect both lipid and protein moieties of LDL from free radical-induced oxidation, inhibiting accumulation of both primary and secondary oxidation products (Kontush and Chapman 2010). The following overview will focus on the impact of HDL on lipid hydroperoxides and other primary products of lipid peroxidation.