New insights into immunological aspects of atherosclerosis

Although atherosclerosis was previously thought to be mainly a degenerative disease, it is now well ascertained that its pathogenesis is inflammatory. This review describes the history of anew atherogenetic concept, including the pivotal role of apoE-knockout mice in understanding the inflammatory background of atherosclerosis. There has been a lack of unequivocal evidence of an important inflammatory component in atherogenesis. This evidence was delivered by a new technique – gene targeting, for the invention of which Mario R. Capecchi, Martin J. Evans and Oliver Smithies received in 2007 the Nobel Prize in Physiology or Medicine. The pivotal stage of atherogenesis is antigen presentation by macrophages to T lymphocytes. This antigen could be a fragment of “digested” by macrophage oxidized low-density lipoproteins, heat shock protein 60, β2-glycoprotein I or fragments of bacterial antigens. For interaction between the immunological cells there must be a presence of CD40 receptor on macrophages and its ligand CD40L on the surface of T lymphocytes. During the interaction between these cells an immunological response type T helper 1 (Th1 – cellular) or T helper 2 (Th2 – humoral) arises. Th1 response and its mediators: interferon-γ, tumor necrosis factor α, interleukin-1, interleukin-12 and interleukin-18 increase atherogenesis, whereas Th2 response and its mediators: interleukin-4, interleukin-5, interleukin-10 and interleukin-13 decrease the development of atherosclerosis. Atherosclerosis is therefore a chronic inflammatory disease, in most cases initiated by hypercholesterolemia. Nowadays, hypercholesterolemia and inflammation are considered as “partners in crime”. The concept of atherosclerosis as inflammatory disease is fairly new, however, it is already considered as an undisputable achievement of science which brings particular therapeutic consequences.