Lipoproteins and protection of the arterial wall against infection: The “response to the threat of infection” hypothesis

Abstract

The exact reason why lipoproteins are found in the arterial intima is not understood. On the basis of recent findings presented in the literature, we are proposing a hypothesis that the accumulation of lipoprotein in the arterial intima is originally a physiological process, part of our defences against infection designed to protect susceptible segments of the arterial wall from microbial invasion. In addition to the intrinsic antimicrobial activities of the deposited lipids, the formation of fibrin-based matrices within the intima is promoted, fibrinolysis is inhibited, the lipid content exerts a vasoconstrictive influence and smooth muscle cells are mobilised into the intima, all these phenomenons being instrumental in fighting off an infectious menace. Oxidized lipids (including oxysterols and lysophosphatidylcholine) resulting from the oxidation of lipoproteins close to sites of infection and inflammation are disseminated through the circulatory system and act as alarm signals at arterial walls, promoting the penetration and retention of lipoproteins in the intimal tissue of the most susceptible segments of the arterial network. Oxidized lipids in the intima constitute part of first-line antimicrobial defences and their presence acts as a signal to immune effector cells (notably macrophages and lymphocytes) which trigger the acquired immune response when foreign antigens are encountered.