Can immunocompetent cells and their cytokines play a role in atherogenesis?
The human atherosclerotic plaque represents a mixture of inflammation, lipid accumulation and fibrosis. Cholesterol deposits are predominantly found in the core of the plaque, which is surrounded by a fibrotic cap. Much of the cholesterol is intracellular in macrophage-derived foam cells, and other macrophages together with T lymphocytes are intermixed with smooth muscle cells in the fibrous cap. Recent studies have shown that cytokines released by inflammatory cells can regulate cell proliferation, cholesterol metabolism, and differentiation of vascular cells. Interferon-gamma, one of the major secretory products of activated T lymphocytes, inhibits smooth muscle proliferation and reduces expression of alpha-actin. This suggests that T cells, by releasing gamma-interferon, may inhibit the formation of arterial stenosis and spasm. Recent animal experiments support this hypothesis by demonstrating that injections of recombinant gamma-interferon reduce arterial intimal lesions after balloon catheter injury. In similar experiments, it was shown that larger intimal lesions develop in T cell-depleted rats and in athymic nude rats. This shows that T cells inhibit the vascular response to injury and supports the notion that gamma-interferon released by these T cells is an important paracrine regulator of arterial cell proliferation. The cytokines, gamma-interferon and TNF, also downregulate scavenger receptor expression in monocyte-derived macrophages, leading to an inhibition of the transformation of these cells into foam cells. Taken together, these data show that cytokines of the immune system are important regulators of cholesterol deposition and cell proliferation in atherogenesis.
Hansson
G K
GK
Gothenburg University, Department of Clinical Chemistry, Sahlgren's Hospital, Sweden.
Stemme
S
S
Geng
Y J
YJ
Holm
J
J
D001161:Arteriosclerosis / Q000209:etiology / Q000503:physiopathology*; D002455:Cell Division; D016207:Cytokines / Q000502:physiology*; D004730:Endothelium, Vascular / Q000473:pathology; D005355:Fibrosis; D006801:Humans; D007121:Immunocompetence; D007249:Inflammation; D050356:Lipid Metabolism; D009131:Muscle, Smooth, Vascular / Q000473:pathology
D016207:Cytokines