Oxidized Low Density Lipoproteins-Do We Know Enough About Them?

Abstract

Since the discovery of oxidized low density lipoprotein (Ox-LDL), over 5,000 articles have appeared on the topic with over 400 articles appearing every year during the past decade. LDL contains esterified polyunsaturated fatty acid containing lipids, such as, phosphatidylcholine (PtdCho) and cholesterol esters (CE). Peroxidation of polyunsaturated fatty acid (PUFA) containing lipids has been known for a long time. Numerous studies have documented that peroxidized lipids as well as products derived from their decomposition, particularly aldehydes, have deleterious biological properties. This concept has been exemplified in the study of atherosclerosis. A plethora of in vitro and animal studies, as well as human epidemiological and correlatory studies, have supported the notion that oxidative processes and the formation of Ox-LDL might contribute to atherosclerosis. Yet the negative outcomes of human clinical trials with α-tocopherol and other antioxidants have convinced even staunch supporters of the hypothesis to take a step backwards and reconsider reasons of their failure and suggest alternative approaches. Ox-LDL is a complex mixture of numerous chemical entities, many of them are yet uncharacterized. Why and how it is formed or its nature in vivo is poorly understood. It is recognized by numerous cell surface receptors, which are ubiquitously expressed in many different cell types. These receptors might perform a variety of functions. In addition, components of Ox-LDL might also have favorable effects that are difficult to dissociate from its pathological effects. In this review, the nature of Ox-LDL and potential problems in inhibiting its formation are discussed.

Developmental Endothelial Locus-1 (Del-1) Inhibits Oxidized Low-Density Lipoprotein Activity by Direct Binding, and Its Overexpression Attenuates Atherogenesis in Mice

“…36 Another reason might be, as we demonstrated in this study, the existence of molecules that inhibit oxLDL activity without affecting oxLDL concentrations that are determined by antioxLDL antibodies. Such conditions have not been taken into consideration in previous anti-oxLDL antibody-based measurement systems.…”

In Vitro Anti-Plasmodium falciparum Properties of the Full Set of Human Secreted Phospholipases A 2

“…Some of the above-listed human sPLA 2 s might be endogenous factors acting against Plasmodium, yet the in vivo relevance of our observations remains to be established. Our studies further highlight a functional interrelationship between sPLA 2 s and lipoproteins, which may act in concert in the pathophysiology of malaria, and possibly in other types of infections and diseases in which lipoproteins play a role (69)(70)(71). Human sPLA 2 s with anti-Plasmodium activity might deserve future consideration as potential therapeutic tools or agents.…”

Characterization of the inhibition of hepatitis C virus entry by In vitro –generated and patient-derived oxidized low-density lipoprotein

“…Most studies investigating the biological effects of oxLDL, including ours, use copper-oxidized LDL because it is thought to share many properties of endogenous oxLDL. 25 However, oxidation likely introduces a multitude of chemical alterations to all parts of the LDL particle, and to what extent these are truly alike in copper oxidized and endogenous oxLDL is unknown. Our observation that the available oxLDL Fig.…”

“…24 oxLDL is a modified form of LDL that is generated early on in the pathogenesis of atherosclerosis, when native LDL deposited in early atherosclerotic lesions (''fatty streaks'') undergoes oxidative modifications. 25 The exact nature and driving forces behind these modifications are incompletely understood, 26 but they allow LDL to be taken up in great quantities by macrophages through an LDLreceptor-independent route creating foam cells, a hallmark of atherosclerotic lesions. 27 Previous work on oxLDL has almost exclusively relied on HCV pseudoparticles (HCVpp), and there may be important differences in the cell-entry properties of HCVpp and full-length HCV particles grown in cell culture (HCVcc).…”