Relationship between autophagy and complete blood count in patient with acute myocardial infarction

Autophagy is a self-protective mechanism of living cells or organisms under various stress conditions. In this study level of autophagy enzyme in patients with coronary artery disease are measured. Then we investigated to effects of autophagy on the hematologic parameters. 66 patients were included in our study. Participants were separated 2 groups: Group 1- patients with acute myocardial infarction (n=36); and Group 2- normal controls patients (n=30). Blood samples of all patients were collected during coronary angiography process. The enzyme-linked immunosorbent assay (ELISA) kit for autophagy related protein 5(ATG5) in the plasma was studied for these two groups of blood sample. Then autophagy level and complete blood count were compared. Age, gender, prevalence of diabetes mellitus, body-mass-index (BMI) and dyslipidemia were similar between the groups. Autophagy levels are significantly different between the groups(11.7±3.4 ng/ml; ; 7.5±3ng/ml ; p < 0.001, respectively). Significant positive correlations were found between level of autophagy and white blood cell count (r = 0.491, p < 0.001), neutrophil /lymphocyte ratio ( r=0.287 , p=0.019) . Significant negative correlations were found between level of autophagy and ejection fraction (r = -0.427, p < 0.001 ). In the present study, the autophagy levels were higher in the patients with coronary artery disease than healthy controls. Serum autophagy levels demonstrated a significant positive correlation with white blood cell count and neutrophil/lymphocyte ratio .An increased autophagy level may be considered as an important activator and marker of the atherosclerotic inflammatory process in CAD.

PDF

___

Ma X, Liu H, Foyil SR et al. Impaired autophagosome clearance contributes to cardiomyocyte death in ischemia/ reperfusion injury. Circulation. 2012;125:3170–81.

Matsui Y, Takagi H, Qu X, et al. Distinct roles of autophagy in the heart during ischemia and reperfusion: roles of AMPactivated protein kinase and Beclin 1 in mediating autophagy. Circ Res. 2007;100:914–22.

Kanamori H, Takemura G, Goto K, et al. The role of autophagy emerging in postinfarction cardiac remodelling. Cardiovasc Res. 2011;91:330–9.

Kanamori H, Takemura G, Goto K, et al. Autophagy limits acute myocardial infarction induced by permanent coronary artery occlusion. Am J Physiol Heart Circ Physiol. 2011; 300:2261–71.

Geng, J., and Klionsky, D.J. The Atg8 and Atg12 ubiquitin-like conjugation systems in macroautophagy. ’Protein modifications: beyond the usual suspects’ review series. EMBO Rep. 2008;9:859–64.

Duffy BK, Gurm HS, Rajagopal V, et al. Usefulness of an elevated neutrophil to lymphocyte ratio in predicting long-term mortality after percutane¬ous coronary intervention. Am J Cardiol. 2006;97:993-6.

Papa A, Emdin M, Passino C et al. Predictive value of elevated neutrophillympho¬cyte lympho¬cyte ratio on cardiac mortality in patients with stable cor¬onary artery disease. Clin Chim Acta. 2008;395:27-31.

Tamhane UU, Aneja S, Montgomery D, et al. Association between admission neutrophil to lymphocyte ratio and outcomes in patients with acute coronary syndrome. Am J Cardiol. 2008;102:653-7.

Kurtul A, Murat SN, Yarlioglues M, et al. Association of platelet-tolymphocyte ratio with severity and complexity of coronary artery disease in patients with acute coronary syndromes. Am J Cardiol. 2014;114:972–8.

Akboga MK, Canpolat U, Yayla C, et al. Association of Platelet to lymphocyte ratio with inflammation and severity of coronary atherosclerosis in patients with stable coronary artery disease. Angiology. 2016;67:89–95.

Gensini GG. A more meaningful scoring system for determining the severity of coronary artery disease. Am J Cardiol. 1983;51:606.

Eriksson EE, Xie X, Werr J,et al. Direct viewing of atherosclerosis in vivo: plaque invasion by leukocytes is initiated by the endothelial selectins. FASEB J. 2001;15:1149-57.

Yan L, Vatner DE, Kim SJ, et al. Autophagy in chronically ischemic myocardium. Proc Natl Acad Sci USA. 2005;102:13807–12.

Matsui Y, Takagi H, Qu X, et al. Distinct roles of autophagy in the heart during ischemia and reperfusion: roles of AMP-activated protein kinase and Beclin 1 in mediating autophagy. Circ Res. 2007;100:914–22.

Gustafsson AB, Gottlieb RA. Autophagy in ischemic heart disease. Circ Res 2009;104: 150–15

Demircan G, Kaplan O, Ozdas SB. Role of autophagy in the progress of coronary total occlusion. Bratisl Lek Listy. 2018;119:103.

Kaplan O.Effect of Autophagy and Apoptosis on the Hematologic Parameters in Patients with Coronary Artery Disease. Am j Cardiol. 2018;121:4.

Takemura G, Miyata S, Kawase Y,et al. Autophagic degeneration and death of cardiomyocytes in heart failure. Autophagy. 2006;2:212–4.

Hein S, Arnon E, Kostin S, et al. Progression from compensated hypertrophy to failure in the pressure-overloaded human heart: structural deterioration and compensatory mechanisms. Circulation. 2003;107:984–91.

Kanamori H, Takemura G, Maruyama R, et al. Functional significance and morphological characterization of starvation-induced autophagy in the adult heart. Am J Pathol. 2009;174:1705–14.

Ozcan Cetin EH, Cetin MS, Aras D, et al. Platelet to lymphocyte ratio as a prognostic marker of in-Hospital and longterm major adverse cardiovascular events in ST-segment elevation myocardial infarction. Angiology. 2016;67:336–45.

Ganley IG, Lam du H, Wang J, et al. ULK1.ATG13.FIP200 complex mediates mTOR signaling and is essential for autophagy. J Biol Chem. 2009; 284:12297–305.

Kim J, Kundu M, Viollet B,et al. AMPK and mTOR regulate autophagy through direct phosphorylation of Ulk1. Nat Cell Biol. 2011;13:132–41.

Egan DF, Shackelford DB, Mihaylova MM, et al. Phosphorylation of ULK1 (hATG1) by AMP-activated protein kinase connects energy sensing to mitophagy. Science 2011;331:456–61.

Stephan JS, Yeh YY, Ramachandran V, et al. The Tor and PKA signaling pathways independently target the Atg1/Atg13 protein kinase complex to control autophagy. Proc Natl Acad Sci USA. 2009;106:17049–54.