Autophagy biomarkers in patients with acute myocardial infarction

Abstract

Abstract Introduction Acute myocardial infarction (AMI) is still one of leading cause for mortality and disability in cardiovascular disease [1]. Autophagy is an intracellular mechanism involved in the elimination and the recycling of proteins and organelles by lysosomes [2]. Autophagy has an important role of critical cellular process for the self-protective degradation mechanism and recycling of cellular components in ischemic events such as AMI and left ventricular remodeling [3]. However, very few studies are evaluated the activity of autophagy and the relationship between autophagy activity and prognosis in patients with AMI. Purpose We aimed to evaluate the activity of autophagy in patients with AMI. Moreover, our study evaluated the associations of autophagy biomarkers with traditional cardiac biomarkers such as CK-MB, Troponin T and NT-proBNP, and echocardiographic left ventricular ejection fraction (LVEF). Methods We prospectively enrolled AMI patients with urgent coronary revascularization and controls who underwent coronary angiography without significant coronary artery stenosis. We obtained the serum of patients from peripheral artery and coronary artery before coronary revascularization. Levels of LC3-II, ATG5, Beclin 1 and M30 were quantified by ELISA in the serum from 22 AMI patients and 19 controls. Associations between autophagy biomarkers and traditional cardiac biomarkers were analyzed by Spearman bivariate correlation analysis. Results There were no significant differences in age, gender, systolic blood pressure, diastolic blood pressure, heart rate and medical history including hypertension, diabetes, dyslipidemia and atrial fibrillation between two groups. AMI patients had significant higher concentrations of autophagy biomarkers such as LC3-II (218.2±47.1 vs. 117.2±28.0 ng/ml; 238.4±60.5 vs. 118.5±27.7 ng/ml; p<0.001), ATG5 (205.6±57.8 vs. 62.9±40.0 ng/ml; 199.5±56.3 vs. 68.4±54.7 ng/ml; p<0.001), and Beclin 1 (225.6±55.1 vs. 123.8±16.6 ng/ml; 222.1±51.4 vs. 115.4±21.4 ng/ml; p<0.001) in peripheral artery and coronary artery, both (Figure 1). M30 of apoptosis level was also significantly higher in AMI patients than in controls (262.0±78.6 vs. 148.4±57.7 ng/ml; 290.4±128.5 vs. 144.5±50.1 ng/ml; p<0.001). Especially, LC3-II and Beclin 1 in coronary artery had strong positive correlations with Troponin T (rho=0.630, p<0.001; rho=0.624, p<0.001, respectively). Conclusions Autophagy biomarkers such as LC3-II, ATG5 and Beclin 1 were significantly higher in AMI patients than in controls. Autophagy biomarkers had significant positive correlations with Troponin T and NT-proBNP as the traditional cardiac biomarkers and negative correlations with LVEF. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT)