ABSTRACT
Accumulation and oxidation of lipoproteins in the extracellular matrix of the artery wall is a key initiating factor in the development of atherosclerosis.1,2 It results in activation of an inflammatory response mediated by what is referred to as the innate component of immunity. This part of the immune system provides a rapid and non-specific defense against invading microorganisms but reacts also with modified self-antigens such as oxidized low-density lipoprotein (LDL) and dying cells. The inflammatory response induced by the innate immune system is believed to play a key role in both plaque growth and the development of plaque vulnerability.3,4 More recently, it has become evident that adaptive immune responses are also critically involved in the disease process. Adaptive immunity is much more complex, specific, and finetuned than innate immunity and, as a consequence, may take several days or even weeks to be fully mobilized. It involves a genetic rearrangement process in immunoblasts, leading to generation of a large number of highly antigen-specific T-and B-cell receptors and antibodies. One important function of adaptive immunity is to modulate the inflammatory activity of the innate immune system in order to mount the most appropriate response for each type of challenge. Accordingly, it has
become clear that the immune system represents an interesting target for development of novel therapies for prevention and treatment of cardiovascular disease.5,6
A schematic overview of the innate and adaptive immune systems is given in Figure 31.1. Our understanding of the functional role of the immune system in atherosclerosis is primarily based on mouse studies in which atherosclerosissusceptible, hypercholesterolemic animals such as ApoE−/− and LDL receptor−/− mice have been cross-bred with mice genetically deficient or transgenically overexpressing specific immune receptors, co-stimulatory factors, and cytokines.
