Unique Antibody Responses to Malondialdehyde-Acetaldehyde (MAA)-Protein Adducts Predict Coronary Artery Disease

Abstract

Malondialdehyde-acetaldehyde adducts (MAA) have been implicated in atherosclerosis. The purpose of this study was to investigate the role of MAA in atherosclerotic disease. Serum samples from controls (n = 82) and patients with; non-obstructive coronary artery disease (CAD), (n = 40), acute myocardial infarction (AMI) (n = 42), or coronary artery bypass graft (CABG) surgery due to obstructive multi-vessel CAD (n = 72), were collected and tested for antibody isotypes to MAA-modifed human serum albumin (MAA-HSA). CAD patients had elevated relative levels of IgG and IgA anti-MAA, compared to control patients (p<0.001). AMI patients had a significantly increased relative levels of circulating IgG anti-MAA-HSA antibodies as compared to stable angina (p<0.03) or CABG patients (p<0.003). CABG patients had significantly increased relative levels of circulating IgA anti-MAA-HSA antibodies as compared to non-obstructive CAD (p<0.001) and AMI patients (p<0.001). Additionally, MAA-modified proteins were detected in the tissue of human AMI lesions. In conclusion, the IgM, IgG and IgA anti-MAA-HSA antibody isotypes are differentially and significantly associated with non-obstructive CAD, AMI, or obstructive multi-vessel CAD and may serve as biomarkers of atherosclerotic disease.

Translational Implications of the Alcohol-Metabolizing Enzymes, Including Cytochrome P450-2E1, in Alcoholic and Nonalcoholic Liver Disease

“…Acetaldehyde has been also shown to be conjugated with numerous proteins including tubulin (Israel, 1997;Jennett, Sorrell, Saffari-Fard, Ockner, & Tuma, 1989;Niemelä et al, 1998Niemelä et al, , 1994Sutti et al, 2014) to activate immune reactions. Critical roles of ALDH2 and CYP2E1 in producing MAA or advanced glycation end product (AGE) adducts and other protein adducts have been suggested (Anderson et al, 2014;Duryee et al, 2005;Jeong et al, 2000;Kwon et al, 2014;Swaminathan, Kumar, Clemens, & Dey, 2013;Thiele et al, 2001). In addition, acetaldehyde can interact with DNA to produce DNA adducts (Brooks et al, 2009;Yu et al, 2010Yu et al, , 2012.…”

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

“…With chronic antigen stimulation, immunoglobulin phenotype patterns would be expected to vary over the course of time and disease. Although anti-MAA antibodies are associated with coronary artery disease [45], these antibody patterns may also be directly pathogenic (IgG and IgA isotypes) and/or have autoimmune characteristics (Fig. 2).…”

“…Similar to ethanol consumption, inhalation of cigarette smoke, which contains both large quantities of AA and by-products that lead to reactive oxygen species production, leads to increased MAA adduction in vivo [54]. In recent years, MAA modification of proteins has been recognized as a pathogenic link between atherosclerosis [45] and classical cardiovascular risk factors that are associated with oxidative stress: hypertension (HTN), hyperlipidemia, diabetes mellitus (DM), tobaccos use, and heavy ethanol consumption. These risk factors along with a potential mechanism are shown in Fig.…”

“…Posttranslational modification of proteins and lipoproteins and the formation of multiple protein adducts, including MDA and MAA, have been associated with the development and progression of atherosclerotic disease [27,45,[55][56][57][58]. MDA-and MAA-modified proteins have been found in the circulation [59,60] and in atherosclerotic lesions [61][62][63] of patients with atherosclerotic disease.…”

“…Although the exact cardiovascular tissue proteins that are MAA modified are unknown, MAA-modified proteins are strongly associated with early atherosclerosis, vascular inflammation, acute myocardial infarction (AMI), and sudden cardiac death after AMI [45]. This has been shown in obese insulin-resistant hyperlipidemic James C. Russell:LA-cp atherosclerotic rats [27] and in human atherosclerotic disease studies [45].…”