Regulation and therapeutic strategies of 4-hydroxy-2-nonenal metabolism in heart disease

Mali, Vishal; Palaniyandi, Suresh S.

doi:10.3109/10715762.2013.864761

Cited by 94 publications

(74 citation statements)

References 123 publications

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“…LDLR −/− is a well-established mouse model used to study atherosclerosis. 4-HNE was identified in mouse atherosclerotic lesions and liver, and levels of 4-HNE were associated with cell death in these tissues [21]. We employed this mouse model to test if EAA-CL and other cardiolipin oxidation products were formed in the liver during the formation of atherosclerotic plaques in the aorta.…”

Section: Resultsmentioning

confidence: 99%

“…Among the complicated oxidation products, lipid electrophiles, including 4-HNE, generated from lipid oxidation have attracted increased attention due to their potential roles in altering protein structures and functions through covalent modification of critical nucleophilic amino acid residues [10,21,22]. Overwhelming evidence indicates that mitochondria play an essential role in ROS generation, lipid peroxidation, and the pleiotropic effects of 4-HNE in various biological processes.…”

Section: Discussionmentioning

confidence: 99%

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Formation of electrophilic oxidation products from mitochondrial cardiolipin in vitro and in vivo in the context of apoptosis and atherosclerosis

Zhong¹,

Lu²,

Xia³

et al. 2014

Redox Biology

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Emerging evidence indicates that mitochondrial cardiolipins (CL) are prone to free radical oxidation and this process appears to be intimately associated with multiple biological functions of mitochondria. Our previous work demonstrated that a significant amount of potent lipid electrophiles including 4-hydroxy-nonenal (4-HNE) was generated from CL oxidation through a novel chemical mechanism. Here we provide further evidence that a characteristic class of CL oxidation products, epoxyalcohol-aldehyde-CL (EAA-CL), is formed through this novel mechanism in isolated mice liver mitochondria when treated with the pro-apoptotic protein t-Bid to induce cyt c release. Generation of these oxidation products are dose-dependently attenuated by a peroxidase inhibitor acetaminophen (ApAP). Using a mouse model of atherosclerosis, we detected significant amount of these CL oxidation products in liver tissue of low density lipoprotein receptor knockout (LDLR −/−) mice after Western diet feeding. Our studies highlight the importance of lipid electrophiles formation from CL oxidation in the settings of apoptosis and atherosclerosis as inhibition of CL oxidation and lipid electrophiles formation may have potential therapeutic value in diseases linked to oxidant stress and mitochondrial dysfunctions.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Formation of electrophilic oxidation products from mitochondrial cardiolipin in vitro and in vivo in the context of apoptosis and atherosclerosis

Zhong¹,

Lu²,

Xia³

et al. 2014

Redox Biology

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show abstract

“…Furthermore, accumulation of lipid peroxidation and 4-HNE in the vitreous were linked to the development of diabetic retinopathy (Mancino et al, 2011;Zhou et al, 2011). More detailed information and data on protein modifications by 4-HNE and their detrimental consequences in different pathologies are available in a series of comprehensive review articles (Ayala et al, 2014;Csala et al, 2015;Dianzani, 2003;Domingues et al, 2013;Esterbauer et al, 1991;Gueraud et al, 2010;Mali and Palaniyandi, 2014;Negre-Salvayre et al, 2008, 2010Niki, 2009;Poli et al, 2008b;Schaur et al, 2015;Shoeb et al, 2014). It should be noted, however, that despite the clear cytotoxicity of 4-HHE and 4-HDDE they have not yet obtained the same recognition as 4-HNE has (Bacot et al, 2003;Bradley et al, 2012;Je et al, 2004;Long et al, 2008;Lovell et al, 2012;Riahi et al, 2010aRiahi et al, , 2010bTanito et al, 2009).…”

Section: Article In Pressmentioning

confidence: 96%

Hormetic and regulatory effects of lipid peroxidation mediators in pancreatic beta cells

Maulucci

Daniel

Cohen

et al. 2016

Molecular Aspects of Medicine

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“…To further assess oxidative stress, immunostaining of 4-HNE, a product of lipid peroxidation (26), was performed in E14.5 hearts (Fig. 1A).…”

Section: Pregestational Diabetes Increases Oxidative Stress In Fetal mentioning

confidence: 99%

Pregestational Diabetes Induces Fetal Coronary Artery Malformation via Reactive Oxygen Species Signaling

Moazzen

Liu

et al. 2014

Diabetes

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Hypoplastic coronary artery disease is a congenital coronary artery malformation associated with a high risk of sudden cardiac death. However, the etiology and pathogenesis of hypoplastic coronary artery disease remain undefined. Pregestational diabetes increases reactive oxygen species (ROS) levels and the risk of congenital heart defects. We show that pregestational diabetes in mice induced by streptozotocin significantly increased 4-hydroxynonenal production and decreased coronary artery volume in fetal hearts. Pregestational diabetes also impaired epicardial epithelialto-mesenchymal transition (EMT) as shown by analyses of the epicardium, epicardial-derived cells, and fate mapping. Additionally, the expression of hypoxia-inducible factor 1a (Hif-1a), Snail1, Slug, basic fibroblast growth factor (bFgf), and retinaldehyde dehydrogenase (Aldh1a2) was decreased and E-cadherin expression was increased in the hearts of fetuses of diabetic mothers. Of note, these abnormalities were all rescued by treatment with N-acetylcysteine (NAC) in diabetic females during gestation. Ex vivo analysis showed that high glucose levels inhibited epicardial EMT, which was reversed by NAC treatment. We conclude that pregestational diabetes in mice can cause coronary artery malformation through ROS signaling. This study may provide a rationale for further clinical studies to investigate whether pregestational diabetes could cause hypoplastic coronary artery disease in humans.Pregestational diabetes is a risk factor for congenital heart defects in infants (1,2). Clinical studies have shown that pregestational diabetes increases the risk of congenital heart defects in the offspring by three-to fivefold compared with nondiabetic pregnancies (1-3). To date, analysis of congenital heart malformation in the newborn is mainly restricted to major cardiac structures, which include the aorta, pulmonary artery, atrioventricular septum, cardiac valves, and myocardium, but coronary arteries are not routinely examined (4). Congenital malformation can occur in the coronary arteries, leading to null coronary artery or hypoplastic coronary artery disease (5). Although null coronary artery is embryonically lethal, hypoplastic coronary artery disease is a rare congenital coronary abnormality defined by malformation of one or more major branches of the coronary arteries with a marked decrease in luminal diameter and length. Hypoplastic coronary artery disease can be asymptomatic but often is associated with myocardial infarction and sudden cardiac death during intense physical activity (6). However, the etiology and pathogenesis of hypoplastic coronary artery disease remain undefined. Furthermore, it is not known whether pregestational diabetes results in coronary artery malformation in offspring. Isolated cases of congenital coronary artery abnormalities have been identified in infants by autopsy. However, whether the mothers of these infants had pregestational diabetes was not disclosed in these reports (7,8). A large multicenter case-control study sho...

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Regulation and therapeutic strategies of 4-hydroxy-2-nonenal metabolism in heart disease

Cited by 94 publications

References 123 publications

Formation of electrophilic oxidation products from mitochondrial cardiolipin in vitro and in vivo in the context of apoptosis and atherosclerosis

Formation of electrophilic oxidation products from mitochondrial cardiolipin in vitro and in vivo in the context of apoptosis and atherosclerosis

Hormetic and regulatory effects of lipid peroxidation mediators in pancreatic beta cells

Pregestational Diabetes Induces Fetal Coronary Artery Malformation via Reactive Oxygen Species Signaling

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