Acrolein-conjugated low-density lipoprotein induces macrophage foam cell formation

Watanabe, Kenta; Nakazato, Yuki; Saiki, Ryotaro; Igarashi, Kazuei; Kitada, Mitsukazu; Ishii, Itsuko

doi:10.1016/j.atherosclerosis.2012.12.020

Cited by 37 publications

(19 citation statements)

References 27 publications

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“…More recently, Tamamizu-Kato et al [99] demonstrated that acrolein markedly impaired the functional integrity of Apo E, an exchangeable anti-atherogenic apolipoprotein when present at a 10-fold molar excess, along with heparin-, lipid-and lipid-receptor-binding; experiments were performed using recombinant Apo E, and immuno-blotting employing an acrolein-lysine-specific antibody. These studies are fully consistent with the detection of acrolein in atherosclerotic lesions [96], and acrolein-modified LDL was also found to induce the generation of foam cells from macrophages [100].…”

Section: Atherosclerosis and Its Cardiovascular Disease Sequelaesupporting

confidence: 86%

Potential Adverse Public Health Effects Afforded by the Ingestion of Dietary Lipid Oxidation Product Toxins: Significance of Fried Food Sources

et al. 2020

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Exposure of polyunsaturated fatty acid (PUFA)-rich culinary oils (COs) to high temperature frying practices generates high concentrations of cytotoxic and genotoxic lipid oxidation products (LOPs) via oxygen-fueled, recycling peroxidative bursts. These toxins, including aldehydes and epoxy-fatty acids, readily penetrate into fried foods and hence are available for human consumption; therefore, they may pose substantial health hazards. Although previous reports have claimed health benefits offered by the use of PUFA-laden COs for frying purposes, these may be erroneous in view of their failure to consider the negating adverse public health threats presented by food-transferable LOPs therein. When absorbed from the gastrointestinal (GI) system into the systemic circulation, such LOPs may significantly contribute to enhanced risks of chronic non-communicable diseases (NCDs), e.g. , cancer, along with cardiovascular and neurological diseases. Herein, we provide a comprehensive rationale relating to the public health threats posed by the dietary ingestion of LOPs in fried foods. We begin with an introduction to sequential lipid peroxidation processes, describing the noxious effects of LOP toxins generated therefrom. We continue to discuss GI system interactions, the metabolism and biotransformation of primary lipid hydroperoxide LOPs and their secondary products, and the toxicological properties of these agents, prior to providing a narrative on chemically-reactive, secondary aldehydic LOPs available for human ingestion. In view of a range of previous studies focused on their deleterious health effects in animal and cellular model systems, some emphasis is placed on the physiological fate of the more prevalent and toxic α,β-unsaturated aldehydes. We conclude with a description of targeted nutritional and interventional strategies, whilst highlighting the urgent and unmet clinical need for nutritional and epidemiological trials probing relationships between the incidence of NCDs, and the frequency and estimated quantities of dietary LOP intake.

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Section: Atherosclerosis and Its Cardiovascular Disease Sequelaesupporting

confidence: 86%

Potential Adverse Public Health Effects Afforded by the Ingestion of Dietary Lipid Oxidation Product Toxins: Significance of Fried Food Sources

et al. 2020

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“…Nε-(3-methylpyridinium)-lysine (MP-Lys), an acrolein derivative, was detected in Apo B of native LDL (Obama et al, 2007). Moreover, acrolein-LDL induced foam cell formation from macrophages, suggesting that acrolein maight contribute to LDL modification, foam cell formation and atherogenesis (Watanabe et al, 2013). …”

Section: Aldehyde-protein Adducts In Atherosclerosismentioning

confidence: 99%

Interaction of aldehydes derived from lipid peroxidation and membrane proteins

Pizzimenti¹,

Ciamporcero²,

Daga³

et al. 2013

Front. Physiol.

272

186

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A great variety of compounds are formed during lipid peroxidation of polyunsaturated fatty acids of membrane phospholipids. Among them, bioactive aldehydes, such as 4-hydroxyalkenals, malondialdehyde (MDA) and acrolein, have received particular attention since they have been considered as toxic messengers that can propagate and amplify oxidative injury. In the 4-hydroxyalkenal class, 4-hydroxy-2-nonenal (HNE) is the most intensively studied aldehyde, in relation not only to its toxic function, but also to its physiological role. Indeed, HNE can be found at low concentrations in human tissues and plasma and participates in the control of biological processes, such as signal transduction, cell proliferation, and differentiation. Moreover, at low doses, HNE exerts an anti-cancer effect, by inhibiting cell proliferation, angiogenesis, cell adhesion and by inducing differentiation and/or apoptosis in various tumor cell lines. It is very likely that a substantial fraction of the effects observed in cellular responses, induced by HNE and related aldehydes, be mediated by their interaction with proteins, resulting in the formation of covalent adducts or in the modulation of their expression and/or activity. In this review we focus on membrane proteins affected by lipid peroxidation-derived aldehydes, under physiological and pathological conditions.

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“…Like HNE, acrolein also readily forms covalent adducts with nucleophilic sites in proteins, lipids and DNA and acrolein-modified proteins have been detected in oxidized LDL [34] and human atherosclerotic lesions [35]. Indeed, the uptake of acrolein-modified LDL by the SR-A1 receptors (scavenger receptor class A type 1) has been implicated in the formation of foam cells, which constitute the characteristics fatty streaks of early atherosclerotic lesions in the affected arteries [36]. …”

Section: Major Carbonyl Compoundsmentioning

confidence: 99%

Oxidative and reductive metabolism of lipid-peroxidation derived carbonyls

Singh

Kapoor

Bhatnagar

2015

Chemico-Biological Interactions

118

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Extensive research has shown that increased production of reactive oxygen species (ROS) results in tissue injury under a variety of pathological conditions and chronic degenerative diseases. While ROS are highly reactive and can incite significant injury, polyunsaturated lipids in membranes and lipoproteins are their main targets. ROS-triggered lipid peroxidation reactions generate a range of reactive carbonyl species (RCS), and these RCS spread and amplify ROS-related injury. Several RCS generated in oxidizing lipids, such as 4-hydroxy trans-2-nonenal (HNE), 4-oxo-2-(E)-nonenal (ONE), acrolein, malondialdehyde (MDA) and phospholipid aldehydes have been shown to be produced under conditions of oxidative stress and contribute to tissue injury and dysfunction by depleting glutathione and other reductants leading to the modification of proteins, lipids, and DNA. To prevent tissue injury, these RCS are metabolized by several oxidoreductases, including members of the aldo-keto reductase (AKR) superfamily, aldehyde dehydrogenases (ALDHs), and alcohol dehydrogenases (ADHs). Metabolism via these enzymes results in RCS inactivation and detoxification, although under some conditions, it can also lead to the generation of signaling molecules that trigger adaptive responses. Metabolic transformation and detoxification of RCS by oxidoreductases prevent indiscriminate ROS toxicity, while at the same time, preserving ROS signaling. A better understanding of RCS metabolism by oxidoreductases could lead to the development of novel therapeutic interventions to decrease oxidative injury in several disease states and to enhance resistance to ROS-induced toxicity.

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Acrolein-conjugated low-density lipoprotein induces macrophage foam cell formation

Cited by 37 publications

References 27 publications

Potential Adverse Public Health Effects Afforded by the Ingestion of Dietary Lipid Oxidation Product Toxins: Significance of Fried Food Sources

Potential Adverse Public Health Effects Afforded by the Ingestion of Dietary Lipid Oxidation Product Toxins: Significance of Fried Food Sources

Interaction of aldehydes derived from lipid peroxidation and membrane proteins

Oxidative and reductive metabolism of lipid-peroxidation derived carbonyls

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