Unique antibody responses to malondialdehyde-acetaldehyde (MAA)-protein adducts predict coronary artery disease.

Harlan R Sayles,Scott W Shurmur,Daniel R Anderson,Walter D Bussey,Michael J Duryee,Robert P Garvin,John Y Um,Carlos D Hunter,Ted R Mikuls,Geoffrey M Thiele,Alexander G Obukhov,Lynell W Klassen

doi:10.1371/journal.pone.0107440

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.

Highlights

Inflammation is thought to be central in the pathogenesis of atherosclerosis [1,2] and acute myocardial infarction (AMI) [3]
Evaluation and comparison of 4 patient groups were undertaken and this study cohort is presented in the Table 1. These four groups included; 1) ‘‘Controls’’ – Patients without any history of coronary artery disease (CAD); 2) ‘‘Non-Obstructive CAD’’ - Patients that presented for cardiac catheterization with chest pain and CAD, but no evidence of an AMI; 3) ‘‘Acute MI’’ - Patients with CAD who presented with an AMI; and, 4) ‘‘Multi-Vessel Obstructive CAD’’ - Patients with severe CAD who presented for coronary artery bypass graft (CABG) surgery
Non-Obstructive CAD and Acute MI patients who were diagnosed with CAD at the time of catheterization, have a lower incidence of ACE inhibitor and statin use compared to patients with known CAD presenting for CABG surgery

Summary

Introduction

Inflammation is thought to be central in the pathogenesis of atherosclerosis [1,2] and acute myocardial infarction (AMI) [3]. The driving mechanism(s) of cardiovascular inflammation is/are uncertain Modification of proteins, such as lipoproteins and the formation of protein-adducts, is one mechanism that has been associated with the development and/or progression of atherosclerotic disease [5,6,7,8,9]. These modified proteins have been found in the circulation [10,11] and in atherosclerotic lesions of patients with atherosclerotic disease [5,8,12,13,14]. The exact direct and/or indirect mechanism(s) by which modified proteins result in cellular dysfunction, [14] immune sensitization, [15,16,17,18,19] tissue inflammation, and atherosclerotic plaque formation and rupture is not fully known

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