[New findings on the pathogenesis of atherosclerosis]

The initial step in the process of atherosclerosis is supposed to be an increased penetration of lipoprotein particles (especially LDL or Lp(a)) into the subendothelial space. It occurs predominantly in regions with endothelial damage. After penetration into intima, LDL particles are oxidized. In endothelial cells, the incompletely oxidized LDL can induce expression of chemotactic factors which attract monocytes from circulation. Formation of adhesive molecules which enable immunocompetent cells to enter the subendothelial space can be simultaneously induced. As a response to stimulation induced by partially oxidized LDL, secretion of colony-forming factors is launched in endothelial cells. These factors induce monocyte to differentiate into macrophages. In subsequent oxidation, strongly oxidized LDL is formed. It is changed not only in the lipoid component but also in the structure of apolipoprotein B100 which brings about additional atherogenic properties. Another form of LDL particle modification is glycation. Absorption of large amounts of modified LDL particles by means of scavenger receptors or by phagocytosis of the lipoprotein complexes with antibody or proteoglycans, macrophages transform into foam cells which are typical for atherosclerotic lesions. In addition, activated macrophages secern various growth factors and cytokins stimulating vascular smooth muscle cells to migrate, proliferate and form extracellular matrix.