Meta-Inflammation In Monocytes Of Patients With Acute Coronary Syndrome

Abstract Background Several studies suggest that an alteration of monocyte metabolism might be implicated in inflammatory diseases. Enhanced glycolysis might be a hallmark of pro-inflammatory monocyte subsets. Improved glycolysis enables the immune cells to generate sufficient ATP and biosynthetic intermediates to carry out its particular effector functions. For macrophages this includes phagocytosis and inflammatory cytokine production. Pyruvate Kinase isozyme M2 (PKM-2) catalyzes the final step of glycolysis producing pyruvate and ATP. Latest studies have shown that a member of Jumonji family (JMJD8) acts as a positive regulator in TNF-induced NF-kB signaling leading to pro-inflammatory pathways in macrophages and is involved in angiogenesis and cellular metabolism through interacting with PKM-2 in endothelial cells. Purpose The aims of the study are to assess the expression of the glycolytic key enzyme PKM-2 in CD14+ monocytes obtained from patients with non-ST-elevation myocardial infarction (NSTEMI) or with stable angina (SA). Furthermore, the expression of JMJD8 was evaluated. Methods 30 patients with NSTEMI and 30 patients with SA were enrolled. Peripheral blood mononuclear cells were obtained from whole blood samples. For cytoplasmatic protein identification, cells were fixed and permeabilized and then incubated with fluorochrome-conjugated mAbs anti-CD14, anti-PKM-2 and anti-JMJD8. For analysis we used Two-tailed Mann-Whitney non parametric Comparison test. Results CD14+ monocytes from NSTEMI patients showed reduced expression of the key glycolytic enzyme PKM-2 as compared to CD14+ monocytes from SA patients (p=0.02) (Figure 1). JMJD8 expression in NSTEMI patients is increased compared with SA patients (p=0.02) (Figure 2). Conclusion This study introduces a role for immune-metabolism in the immunity dysregulation described in ACS patients and provides novel insights into the mechanisms responsible for coronary instability. Taking their potential interaction into account, our data suggest that in acute setting glycolysis key enzyme PKM2 expression is downregulated. Besides, JMJD8 protein levels increase in NSTEMI patients acting as potential limiting factor of PKM2 function. Moreover, our data propose the potential roles of immune-metabolism to detect novel therapeutic targets, associated with an accurate patient stratification based on immune-metabolic profiles, for prevention and treatment of atherosclerosis, in the perspective of a personalized medicine approach. Funding Acknowledgement Type of funding source: Private hospital(s). Main funding source(s): Fondazione Policlinico A. Gemelli