Free Radical Biology and Medicine

2015

DOI: 10.1016/j.freeradbiomed.2015.09.003

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Aldehyde-modified proteins as mediators of early inflammation in atherosclerotic disease

Derrick T. Antoniak

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Michael J. Duryee

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et al.

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Acetaldehyde1

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Cited by 42 publications

(47 citation statements)

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“…Our study showed a significant increase in the formation of anti-MAA IgA in serum of subjects with AUD who also smoke cigarettes. Previously published studies also report higher levels of anti-MAA IgA in the sera of atherosclerotic patients (Antoniak et al, 2015). Here, for the first time, we measured elevated anti-MAA IgA in serum of AUD subjects who smoke cigarettes.…”

Section: Discussionmentioning

confidence: 70%

Malondialdehyde–Acetaldehyde (MAA) Protein Adducts Are Found Exclusively in the Lungs of Smokers with Alcohol Use Disorders and Are Associated with Systemic Anti‐MAA Antibodies

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et al. 2017

Alcoholism Clin & Exp Res

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Background Malondialdehyde (MDA) and acetaldehyde (AA) exist following ethanol metabolism and tobacco pyrolysis. As such, lungs of individuals with alcohol use disorders (AUD) are a target for the effects of combined alcohol and cigarette smoke metabolites. MDA and AA form a stable protein adduct, malondialdehyde-acetaldehyde (MAA) adduct, known to be immunogenic, profibrotic, and proinflammatory. MAA adduct is the dominant epitope in anti-MAA antibody formation. We hypothesized that MAA-adducted protein forms in lungs of those who both abuse alcohol and smoke cigarettes, and that this would be associated with systemically elevated anti-MAA antibodies. Methods Four groups were established: AUD subjects who smoked cigarettes (+AUD/+smoke), smokers without AUD (−AUD/+smoke), AUD without smoke (+AUD/−smoke), and non-AUD/nonsmokers (−AUD/−smoke). Results We observed a significant increase in MAA adducts in lung cells of +AUD/+smoke vs. −AUD/−smoke. No significant increase in MAA adducts was observed in −AUD/+smoke or in +AUD/−smoke compared to −AUD/−smoke. Serum from +AUD/+smoke had significantly increased levels of circulating anti-MAA IgA antibodies. After one week of alcohol that MAA-adducted protein is formed in the lungs of those who smoke cigarettes and abuse alcohol, leading to a subsequent increase in serum IgA antibodies. MAA-adducted proteins could play a role in pneumonia and other diseases of the lung in the setting of AUD and smoking.

“…Our study showed a significant increase in the formation of anti-MAA IgA in serum of subjects with AUD who also smoke cigarettes. Previously published studies also report higher levels of anti-MAA IgA in the sera of atherosclerotic patients (Antoniak et al, 2015). Here, for the first time, we measured elevated anti-MAA IgA in serum of AUD subjects who smoke cigarettes.…”

Section: Discussionmentioning

confidence: 70%

Malondialdehyde–Acetaldehyde (MAA) Protein Adducts Are Found Exclusively in the Lungs of Smokers with Alcohol Use Disorders and Are Associated with Systemic Anti‐MAA Antibodies

¹

,

²

,

³

et al. 2017

Alcoholism Clin & Exp Res

Self Cite

View full text Add to dashboard Cite

Background Malondialdehyde (MDA) and acetaldehyde (AA) exist following ethanol metabolism and tobacco pyrolysis. As such, lungs of individuals with alcohol use disorders (AUD) are a target for the effects of combined alcohol and cigarette smoke metabolites. MDA and AA form a stable protein adduct, malondialdehyde-acetaldehyde (MAA) adduct, known to be immunogenic, profibrotic, and proinflammatory. MAA adduct is the dominant epitope in anti-MAA antibody formation. We hypothesized that MAA-adducted protein forms in lungs of those who both abuse alcohol and smoke cigarettes, and that this would be associated with systemically elevated anti-MAA antibodies. Methods Four groups were established: AUD subjects who smoked cigarettes (+AUD/+smoke), smokers without AUD (−AUD/+smoke), AUD without smoke (+AUD/−smoke), and non-AUD/nonsmokers (−AUD/−smoke). Results We observed a significant increase in MAA adducts in lung cells of +AUD/+smoke vs. −AUD/−smoke. No significant increase in MAA adducts was observed in −AUD/+smoke or in +AUD/−smoke compared to −AUD/−smoke. Serum from +AUD/+smoke had significantly increased levels of circulating anti-MAA IgA antibodies. After one week of alcohol that MAA-adducted protein is formed in the lungs of those who smoke cigarettes and abuse alcohol, leading to a subsequent increase in serum IgA antibodies. MAA-adducted proteins could play a role in pneumonia and other diseases of the lung in the setting of AUD and smoking.

“…ICL crosslinks can lead to genotoxic effects due to DNA damage and protein adducts can disrupt cellular signaling and result in protein aggregation and protein unfolding responses. These effects have been implicated in pathological processes such as myocardial infarction and atherosclerosis [35–39]. …”

Section: Acetaldehydementioning

confidence: 99%

Aldehyde dehydrogenase 2 in aplastic anemia, Fanconi anemia and hematopoietic stem cells

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2016

Molecular Genetics and Metabolism

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Maintenance of the hematopoietic stem cell (HSC) compartment depends on the ability to metabolize exogenously and endogenously generated toxins, and to repair cellular damage caused by such toxins. Reactive aldehydes have been demonstrated to cause specific genotoxic injury, namely DNA interstrand cross-links. Aldehyde dehydrogenase 2 (ALDH2) is a member of a 19 isoenzyme ALDH family with different substrate specificities, subcellular localization, and patterns of expression. ALDH2 is localized in mitochondria and is essential for the metabolism of acetaldehyde, thereby placing it directly downstream of ethanol metabolism. Deficiency in ALDH2 expression and function are caused by a single nucleotide substitution and resulting amino acid change, called ALDH2*2. This genetic polymorphism affects 35–45% of East Asians (about ~560 million people), and causes the well-known Asian flushing syndrome, which results in disulfiram-like reactions after ethanol consumption. Recently, the ALDH2*2 genotype has been found to be associated with marrow failure, with both an increased risk of sporadic aplastic anemia and more rapid progression of Fanconi Anemia. This review discusses the unexpected interrelationship between aldehydes, ALDH2 and hematopoietic stem cell biology, and in particular its relationship to Fanconi anemia.

“…Antibodies to MAA-LDL and HSP60 are both associated with atherosclerosis and they are both produced under similar stressed conditions [13,16]. In our previous study, we identified natural IgM antibodies that recognize MAA-LDL from human umbilical cord blood [3].…”

Section: Introductionmentioning

confidence: 97%

Humoral immune response to heat shock protein 60 of Aggregatibacter actinomycetemcomitans and cross-reactivity with malondialdehyde acetaldehyde-modified LDL

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et al. 2020

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Atherosclerosis is a chronic inflammatory disease and major cause of mortality worldwide. One of the crucial steps for atherosclerotic plaque development is oxidation of low-density lipoprotein (LDL). Through the oxidation, highly immunogenic epitopes are created and the immune system is activated. Association between atherosclerosis and periodontal diseases is well documented, and one of the main oral pathogens common in periodontitis is Aggregatibacter actinomycetemcomitans (Aa). Heat shock protein 60 (HSP60) is an important virulence factor for Aa bacteria and a strong activator of the immune system. Cross-reactivity of HSP60 and oxidized LDL (OxLDL) antibodies could be a potential mechanism in the progression of atherosclerosis and one possible link between atherosclerosis and periodontitis. Human plasma samples from neonates and mothers were analyzed to determine if antibody titer to Aa-HSP60 protein is already present in newborns. Further objectives were to characterize antibody response in Aa-HSP60 immunized mice and to determine possible antibody cross-reaction with oxidized LDL. We demonstrated that newborns already have IgM antibody levels to Aa-HSP60. We also showed that in mice, Aa-HSP60 immunization provoked IgG and IgM antibody response not only to Aa-HSP60 but also to malondialdehyde acetaldehyde-modified LDL (MAA-LDL). Competition assay revealed that the antibodies were specific to Aa-HSP60 and cross-reacted with MAA-LDL. Our results suggest a possibility of molecular mimicry between Aa-HSP60 and MAA-LDL, making it intriguing to speculate on the role of HSP60 protein in atherosclerosis that manifests at young age.

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