In:
European Heart Journal, Oxford University Press (OUP), Vol. 41, No. 33 ( 2020-09-01), p. 3156-3165
Abstract:
Low-grade endotoxaemia is detectable in human circulation but its role in thrombosis is still unclear. Methods and results 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 & lt; 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 & lt; 0.001] and correlated with LPS (Rs = 0.585; P & lt; 0.001). Escherichia coli DNA was positive in 34% of STEMI vs. 12% of SA and 4% of controls (P & lt; 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. Conclusion 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.
Type of Medium:
Online Resource
ISSN:
0195-668X
,
1522-9645
DOI:
10.1093/eurheartj/ehz893
Language:
English
Publisher:
Oxford University Press (OUP)
Publication Date:
2020
detail.hit.zdb_id:
2001908-7
