Mechanisms of the effect of systemic endotoxinemia on development and course of atherosclerosis at cell, systemic and body levels

Abstract

Complications of atherosclerosis, such as stroke and myocardial infarction, has taken a lead among causes of death in developed countries. Multiple hypotheses of atherogenesis exist. The review of 60 reports enables tracking the evolution of understanding the pathogenesis of atherosclerotic diseases, induction of atherogenesis, and risks for atherosclerosis progression. Absolutization of one of them has resulted in predomination of the cholesteric theory of atherosclerosis. Emergence of evidence for participation of viruses and gram-negative bacteria in progression of atherosclerosis allowed atherogenesis to be considered from the standpoint of inflammation (as confirmed by numerous studies). This review focuses on cellular mechanisms, ways of macrophage activation, effects of inflammatory cytokines on arterial smooth muscle cells and endotheliocytes from a position of the inflammation theory of atherosclerosis. Based on current reports, atherogenic mechanisms of endotoxin effects are described as effects of a unique lipopolysaccharide capable for induction of inflammation. The endotoxin concept of atherogenesis is essentially a current stage of the inflammation theory of atherosclerosis. The author described mechanisms of the endotoxin effect on endotheliocytes, monocytes, and arterial smooth muscles cells. Examples of recent studies demonstrated the role of endotoxin in the pathology of cardiovascular diseases on a cell model with the human saphenous vein and on different strains of knockout mice. Data from human studies are presented, including the only population-based study by Bruneck. Possible interrelations of lipid and lipopolysaccharide metabolism based on single transport mechanisms are described. Difficulties of measuring endotoxin concentration in the systemic circulation are related with insufficient informative value and accuracy of available tests. Characteristics of different tests for measuring the LPS concentration and the activity of antiendotoxin immunity were compared, including the LAL-test, micro-LAL-test, LPS-test-ELISA, EAA test, SOIS-method, and ENA.