Prognostic Importance of Systemic Endotoxinemia Indicators in Atherogenesis
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Numerous studies have indicated a close relationship between lipid metabolism disorders and the inflammatory component of atherogenesis. Excess endotoxin (ET) in the general circulation can induce chronic inflammation, and its role in atherogenesis is difficult to overestimate. The involvement of lipopolysaccharide (LPS) in atherogenesis in humans has been studied without assessing the morphological changes in the structure of the vascular wall. It seemed therefore of importance to study the dynamics of the systemic endotoxinemia (SEE) parameters as probable markers of atherosclerosis in association with a progression of morphological changes in the arterial wall. A total of 104 volunteers were examined. The patients had lipid profile abnormalities without clinical manifestations of atherosclerosis, reported themselves to be healthy, and belonged to the moderate risk category (2–4%) on the SCORE scale. A Control group (n = 9) comparable the patients by sex and age. All subjects underwent a duplex scanning of extracranial brachiocephalic arteries (BCA) and a venous blood testing for lipid profile and SEE parameters, including ET, antibodies to the hydrophobic and hydrophilic part of the LPS molecule, and their concentration ratio. The patients were divided into three groups based on the structural changes detected in the arterial wall by ultrasound testing: no morphological change in the BCA (Normal), a thickening of the intima–media complex (TIM), and identified atherosclerotic plaque (ASP). Patients of the ASP group have a significantly higher ET concentration and a reduced activity of anti-ET immunity (AEI) as compared with the accepted reference values and values observed in the TIM group. ET level was not increased, but the AEI activity was reduced in the TIM group, as well as in the Control group. All SEE parameters were within their normal ranges in the Normal group. The main risk factors in assessing the risk for detecting atherosclerotic plaque of the BCA were an age over 55 years and a decrease in antibodies to the hydrophobic part of the LPS molecule below 163 c. u. o. d. Significant differences observed in SEE parameters between patient groups made it possible to assume that an increase in blood LPS concentration and a decrease in AEI activity are risk factors for atherosclerosis.
Keywords:systemic endotoxinemia atherogenesis atherosclerosis endotoxin risk factors inflammation lipopolysaccharide anti-endotoxin immunity cholesterol lipid profile
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Conflict of interests. The authors declare that they have no real or potential conflict of interest with respect to publication of this article.
Statement of compliance with standards of research involving humans as subjects. All studies were in accordance with the biomedical ethical standards of the 1964 Helsinki Declaration and its later amendments and were approved by the Local Ethics Committee at the Institute of General Pathology and Pathophysiology (Moscow). All participants voluntarily gave their written informed consent for participation after being informed about potential risks and benefits and the study procedure.
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