Association of Circulating Autophagy Proteins ATG5 and Beclin 1 with Acute Myocardial Infarction in a Case-Control Study

Abstract

<b><i>Introduction:</i></b> Acute myocardial infarction (AMI) is a main contributor of sudden cardiac death worldwide. The discovery of new biomarkers that can improve AMI risk prediction meets a major clinical need for the identification of high-risk patients and the tailoring of medical treatment. Previously, we reported that autophagy a highly conserved catabolic mechanism for intracellular degradation of cellular components is involved in atherosclerotic plaque phenotype and cardiac pathological remodeling. The crucial role of autophagy in the normal and diseased heart has been well described, and its activation functions as a pro-survival process in response to myocardial ischemia. However, autophagy is dysregulated in ischemia/reperfusion injury, thus promoting necrotic or apoptotic cardiac cell death. Very few studies have focused on the plasma levels of autophagy markers in cardiovascular disease patients, even though they could be companion biomarkers of AMI injury. The aims of the present study were to evaluate (1) whether variations in plasma levels of two key autophagy regulators autophagy-related gene 5 (ATG5) and Beclin 1 (the mammalian yeast ortholog Atg6/Vps30) are associated with AMI and (2) their potential for predicting AMI risk. <b><i>Methods:</i></b> The case-control study population included AMI patients (<i>n</i> = 100) and control subjects (<i>n</i> = 99) at high cardiovascular risk but without known coronary disease. Plasma levels of ATG5 and Beclin 1 were measured in the whole population study by enzyme-linked immunosorbent assay. <b><i>Results:</i></b> Multivariate analyses adjusted on common cardiovascular factors and medical treatments, and receiver operating characteristic curves demonstrated that ATG5 and Beclin 1 levels were inversely associated with AMI and provided original biomarkers for AMI risk prediction. <b><i>Conclusion:</i></b> Plasma levels of autophagy regulators ATG5 and Beclin 1 represent relevant candidate biomarkers associated with AMI.