Abstract 153: Gut Microbiota-derived Lipolysaccarides Are Enhnaced in the Coronary Thrombi of Patients With Myocardial Infarction

Abstract

Background: Gut microbiota seems to be implicated in the athero-thrombotic process. Its relationship with coronary thrombosis has never been investigated. Methods: Serum levels of bacterial lipopolysaccharides (LPS) against Escherichia Coli (EC) and EC DNA amplification by polymerase chain reaction, plasma sP-selectin, a marker of platelet activation, and zonulin, a marker of gut permeability, were measured in patients with ST-elevation myocardial infarction (STEMI) (n=50) or stable coronary disease (SA) (n=50) and controls (n=50). Serum LPS and sP-selectin were also measured in coronary thrombi and coronary blood of patients with STEMI and stable coronary disease, respectively. Immuno-histochemical analysis was performed in coronary thrombi of 12 STEMI patients. Finally, in vitro study was undertaken to evaluate if LPS stimulate leucocyte-platelet interaction. Results: Compared to controls, patients with SA and STEMI had higher systemic levels of LPS (p<0.001), sP-Selectin (p<0.001) and zonulin (p<0.001); these variables were higher in STEMI versus SA (p<0.001). LPS was significantly associated with serum zonulin (β=0.421; p<0.001), and sP-Selectin (Rs=0.501; p<0.001). Analysis of DNA Escherichia coli showed positivity in 10% of patients with coronary heart disease and no positivity in controls. Immuno-histochemical analysis of coronary thrombi showed positivity for leucocyte TLR4 and Cathepsin G (70% and 100% respectively). In vitro study showed that leucocyte incubation with LPS elicited formation of platelet aggregates, which were blunted by an inhibitor of Cathepsin G. Conclusion: Bacterial LPS is detected in coronary thrombi of STEMI patients and may be implicated in the thrombotic process via leucocyte-mediated platelet activation.