Chapter 10 – Oxidized High-Density Lipoprotein: Friend or Foe

High-density lipoprotein (HDL) is considered to be a major anti-atherogenic particle that inhibits conversion of low-density lipoprotein (LDL) into its oxidized form (oxLDL), reduction in the vasoregulatory function, and formation of foam cells. In in vitro experiments, the HDL particle is found to be more vulnerable to oxidative modification than LDL. In addition, recent attentive investigations of clinical specimens have shown that HDL from coronary artery disease and dyslipidemia subjects has a higher sensitivity to lipid oxidation, and that levels of plasma-oxidized HDL (oxHDL) in patients with atherosclerosis, diabetes mellitus, and renal failure are significantly higher, compared with those from healthy donors. Numerous studies using potential oxidants moreover suggest that the oxidative modification of HDL reduces its intrinsic beneficial properties, such as reverse cholesterol transport and antioxidant property, and progressively participates in the development of atherosclerosis through appearance of the pro-inflammatory and cytotoxic effects. By contrast, we recently found that 4-hydroxy-2-nonenal, which is generated during oxidation of HDL, induces cross-linking of apoproteins and upregulates antioxidant enzymes such as aldo-keto reductase (AKR) 1C1 and AKR1C3. In this chapter, we introduce the current literature on clinical relevance of oxHDL to vascular-related diseases, and the structural and functional alterations in HDL due to treating with oxidants. In addition, on the basis of the oxidation-elicited functional changes in HDL and cellular responses to the oxHDL treatment, we discuss whether oxHDL is a causal factor, like oxLDL, or a protective factor for the development of atherosclerosis.