Regulation of leucocyte-endothelial interactions of special relevance to atherogenesis.
1. The cellular events underlying atherosclerosis include the accumulation of lipid-laden monocytes in the neointima. This process is associated with the expression of adhesion proteins and chemokines by the endothelium, in a manner similar to that seen after the administration of pro-inflammatory cytokines to endothelial cells. 2. The processes that limit endothelial responses to proinflammatory cytokines are, therefore, the subject of this paper. Evidence is presented that the cytokine TGF-beta exerts a tonic inhibitory influence on endothelial responses. Furthermore, the smooth muscle cells adjacent to endothelial cells have a similar effect to exogenous TGF-beta and this suggests that these two cells form a functional interactive unit. Finally, the atheroprotective lipid fraction, high-density lipoproteins (HDL), also inhibits endothelial activation. The mechanism of effect of HDL that appears separate from its traditional role in cholesterol transport may yield novel insights into atheroprotection.
Vadas
M A
MA
Hanson Centre for Cancer Research, Adelaide, South Australia, Australia.
Gamble
J R
JR
Rye
K
K
Barter
P
P
D000818:Animals; D001161:Arteriosclerosis / Q000097:blood / Q000209:etiology* / Q000473:pathology; D002448:Cell Adhesion / Q000502:physiology; D004730:Endothelium, Vascular / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D007375:Interleukin-1 / Q000378:metabolism; D017270:Lipoprotein(a) / Q000097:blood; D008075:Lipoproteins, HDL / Q000097:blood; D009000:Monocytes / Q000378:metabolism / Q000473:pathology*; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D016212:Transforming Growth Factor beta / Q000378:metabolism
D007375:Interleukin-1; D017270:Lipoprotein(a); D008075:Lipoproteins, HDL; D016212:Transforming Growth Factor beta