Endotoxin is a compound developed by pathogens such as bacteria. One of these is lipopolysaccharide, a component of the external cell membrane of Gram-negative bacteria.
Endotoxins are responsible for the clinical effects of some diseases. In fact, these substances can act as a barrier against antibacterial drugs, such as antibiotics, limiting their effect.
On the other hand, lipopolysaccharide is a powerful inducer of inflammation, capable of activating the immune response.
This substance is abundant in the human intestine and, despite being toxic and harmful, it can pass in small quantities into the circulation, causing what is known as metabolic endotoxemia.
Previously, different studies have demonstrated the presence of significant concentrations of lipopolysaccharide in patients with atherosclerotic disease, diabetes and in obese subjects.
However, there are also different defense mechanisms that tend to remove lipopolysaccharide from the circulation.
A new study, published in the European Heart Journal, sought to clarify the role of endotoxemia, albeit of a low degree, in the formation of thrombi.
The authors measured the blood concentration of lipopolysaccharide and other specific markers, such as soluble P-selectin, a platelet activation index, and zonulin, a substance that indicates the level of intestinal permeability.
These dosages were made on samples collected not only from peripheral veins, but also from coronary thrombi and from blood collected inside the coronaries.
The study included 50 patients with myocardial infarction and two other reference groups that included 50 patients with stable angina and 50 control subjects.
The results of the study showed higher concentrations of lipopolysaccharide and P-selectin in the coronary thrombi of patients with myocardial infarction, compared to the coronary blood samples of patients with stable angina and to the peripheral blood samples of the control subjects.
Zonulin was also detected at higher concentrations in patients with myocardial infarction, compared to the other two groups. It is important to observe that lipopolysaccharide concentrations were related to those of zonulin.
The study also assessed the presence of DNA from Escherichia coli, demonstrating a prevalence in infarcted patients (34%) compared to the other two groups (stable Angina 12%, controls 4%).
The authors have also added to this clinical study a research conducted in mice, in order to evaluate whether the lipopolysaccharide of Escherichia coli had prothrombotic properties.
They thus injected Escherichia coli lipopolysaccharide into mice, until they reached the same concentrations found in the coronary thrombi of subjects with myocardial infarction. The result was a greater arterial thrombosis and platelet activation.
This study showed as patients with myocardial infarction and ST elevation have greater intestinal permeability, allowing the passage of a bacterial lipopolysaccharide into the circulation. This component could then facilitate the formation of coronary thrombi probably through an interaction between inflammatory cells and platelets.
For many years, inflammatory indices have been considered as risk factors for myocardial infarction. Inflammation characterizes all stages of the formation of the atherosclerotic lesion that precedes myocardial infarction, as well as plaque rupture and the post-infarct repair phase, with remodeling of the infarcted heart.
This research seems to confirm the central role of inflammatory phenomena in the pathogenesis of myocardial infarction. Nevertheless, it opens a completely new perspective in the vision of prothrombotic effects of inflammation, with relevant implications in prevention and treatment of coronary heart disease and, more generally, of thrombotic diseases.
The authors do not rule out the possibility that platelet activation may also occur as a consequence of systemic inflammation, and that lipopolysaccharide contributes to thrombus growth with a mechanism involving coagulation and endothelial activation.
They conclude by proposing for the future the dosage of lipopolysaccharide to stratify the risk of atherothrombosis. An interesting perspective, but that certainly needs to be validated in specifically designed studies.
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