What's new in the pathology of atherosclerosis?
Intimal smooth muscle cell proliferation has been known to be the key event in the development of advanced lesions of atherosclerosis. Since the important role of macrophages in the lipoprotein metabolism has been detected, however, current interest focuses on the macrophage reaction in the arterial wall. Animal experiments have shown that blood monocytes become attached to certain endothelial areas and enter the intima, where they are transformed to macrophages. Subendothelial infiltration of monocytes is the earliest cellular event in the formation of fatty streaks. Transformed to macrophages, they incorporate LDL by receptor-mediated endocytosis and are thus transformed to foam cells. The majority of foam cells in the atherosclerotic plaque is derived from macrophages. Furthermore, the importance of macrophages in the regulation of the lipoprotein metabolism and cholesterol homeostasis is increasingly attributed to their secretory capacities. It has been shown in vitro that they can secrete apolipoprotein E which associates with cholesterol and HDL to form a lipoprotein complex, which targets resecreted cholesterol to the liver cells. Recently, apolipoprotein E secretion of macrophages has also been demonstrated immunohistologically in the human atherosclerotic plaque. Cell culture investigations revealed that macrophages secrete different growth factors for fibroblasts and smooth muscle cells. So they are probably able, among other factors, to initiate smooth muscle cell proliferation in the intima. While smooth muscle cell proliferation and matrix components in the arterial wall had occupied the center of interest in previous investigations, the current focus on the cellular reactions of endothelial cells and monocytes/macrophages, especially in the early stages of atherosclerotic plaque formation, seems well justified.
Roessner
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A
Gerhard-Domagk-Institut für Pathologie, Westfälische Wilhelms-Universität Münster, FRG.
Schmitz
G
G
Sorg
C
C
D000818:Animals; D001161:Arteriosclerosis / Q000503:physiopathology*; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000503:physiopathology; D006801:Humans; D008264:Macrophages / Q000378:metabolism / Q000502:physiology*