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Eur Heart J. 2020 Jan 3. pii: ehz893. doi: 10.1093/eurheartj/ehz893. [Epub ahead of print]

Low-grade endotoxaemia enhances artery thrombus growth via Toll-like receptor 4: implication for myocardial infarction.

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Department of Medical-Surgical Sciences and Biotechnologies, Sapienza University of Rome, Corso della Repubblica 79, Latina 04100, Italy.
Mediterranea Cardiocentro, via Orazio 2, Napoli 80122, Italy.
IRCCS NeuroMed, via Atinense 18, Pozzilli 86077, Italy.
Department of Cardiovascular, Respiratory, Nephrology, Anesthesiology and Geriatric Sciences, Sapienza University of Rome, Viale del Policlinico 155, Rome 00161, Italy.
Department of Clinical, Internal Medicine, Anesthesiology and Cardiovascular Sciences, Sapienza University of Rome, Viale del Policlinico 155, Rome 00161, Italy.
Department of Radiological, Oncological and Pathological Sciences, Sapienza University of Rome, Viale del Policlinico 155, Rome 00161, Italy.
Institute of Cardiology, Catholic University of the Sacred Heart, Largo Francesco Vito 1, Rome 00168, Italy.
Interventional Cardiology Unit, Santa Maria Hospital, Viale Tristano di Joannuccio, Terni 05100, Italy.



Low-grade endotoxaemia is detectable in human circulation but its role in thrombosis is still unclear.


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). Experimental study was carried out in mice to assess if Escherichia coli-LPS (E. coli-LPS) possess thrombotic property. 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.


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.


LPS; Myocardial infarction; Platelets; Thrombosis


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