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Low-grade Endotoxaemia Enhances Artery Thrombus Growth via Toll-like Receptor 4: Implication for Myocardial Infarction

1Sapienza University of Rome, Department of Clinical, Internal Medicine, Anesthesiology and Cardiovascular Sciences, Rome, Italy, 2Sapienza University of Rome, Rome, Italy, 3Santa Maria Hospital, Terni, Italy

Abstract Number: OC 01.2

Meeting: ISTH 2020 Congress

Theme: Arterial Thromboembolism » Acute Coronary Syndromes

Background: Escherichia Coli (EC) lipopolysaccharide, which is a component of gut microbiota, is detectable in human circulation at concentrations potentially eliciting platelet aggregation; however, its role in thrombosis is still unclear.

Aims: To evaluate if low-grade endotoxemia by EC in patients with coronary heart disease may favour thrombus growth at site of coronary unstable plaques.

Methods: We measured serum lipopolysaccharide (LPS) concentration, soluble P-selectin (sP-selectin), a marker of platelet activation, and zonulin, a marker of gut permeability, in peripheral circulation, coronary thrombi, and intracoronary blood of patients with ST-elevation myocardial infarction (STEMI, n = 50) and stable angina (SA) (n = 50), respectively, and in controls (n = 50).

Results: Coronary thrombi from STEMI showed higher concentrations of LPS, sP-selectin vs. intracoronary blood of SA and peripheral blood of controls (P < 0.001). Zonulin was higher in STEMI compared to the other two groups [4.57 (3.34-5.22); 2.56 (0.41-4.36); 1.95 (1.22-2.65) ng/mL; P < 0.001] and correlated with LPS (Rs = 0.585; P < 0.001). Escherichia coli DNA was positive in 34% of STEMI vs. 12% of SA and 4% of controls (P < 0.001). In a subgroup of 12 STEMI, immunohistochemical analysis of coronary thrombi showed positivity for leucocyte Toll-like receptor 4 (TLR4), cathepsin G, and LPS from E. coli in 100%, 80%, and 25% of samples, respectively. E. coli-LPS injected in mice to reach LPS concentrations like those detected in coronary thrombi was associated with enhanced artery thrombosis and platelet activation, an effect blunted by TLR4 inhibitor co-administration. In vitro study demonstrated that LPS from E. coli enhanced platelet aggregation via TLR4-mediated leucocyte cathepsin G activation.

Conclusions: ST-elevation myocardial infarction patients disclose an enhanced gut permeability that results in LPS translocation in human circulation and eventually thrombus growth at site of artery lesion via leucocyte-platelet interaction.

To cite this abstract in AMA style:

Nocella C, Carnevale R, Sciarretta S, Cammisotto V, Valenti V, Calvieri C, Frati G, D'Amati G, Cangemi R, Arrivi A, Dominici M, Mangeri E, Gaudio C, Tanzilli G, Violi F. Low-grade Endotoxaemia Enhances Artery Thrombus Growth via Toll-like Receptor 4: Implication for Myocardial Infarction [abstract]. Res Pract Thromb Haemost. 2020; 4 (Suppl 1). https://abstracts.isth.org/abstract/low-grade-endotoxaemia-enhances-artery-thrombus-growth-via-toll-like-receptor-4-implication-for-myocardial-infarction/. Accessed November 29, 2023.

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