The inflamed plaque: cytokine production and cellular cholesterol balance in the vessel wall.
Although the concept that inflammation plays a role in the biology of atherosclerosis is now well accepted, the basic feature of the arterial lesion remains the accumulation of clusters of foam cells. These clusters are the consequence of the enhanced recruitment of monocytes in the vessel wall induced by the hyperlipidemia and of the disproportionate accumulation of lipids in the cytoplasm of macrophages deriving from monocytes. Ultimately, every molecular force and pathway with modulating activity over the developing lesion will have to act on a convergence point with factors regulating cholesterol balance in the macrophage. Consistent with this view is the recent report that cytokines, such as tumor necrosis factor-alpha, can influence the expression of the scavenger receptor, whereas interferon-gamma can inhibit adenosine triphosphate-binding cassette transporter-1, the main effector of cholesterol efflux in the peripheral cell. Conversely, recent data have shown that primary alterations in macrophage cholesterol balance, such as those produced by the total absence of acylcoenzyme A:cholesterol acyltransferase-1, may determine local changes compatible with the activation of inflammatory pathways. In this brief review, we discuss some of the convergence points between inflammation and cholesterol balance, and we highlight the additional therapeutic targets suggested by these new developments in vascular biology.
Fazio
S
S
Department of Medicine, Division of Cardiovascular Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-6300, USA. sergio.fazio@mcmail.vanderbilt.edu
Linton
M F
MF
D000818:Animals; D001161:Arteriosclerosis / Q000209:etiology / Q000378:metabolism; D002114:Calcinosis / Q000150:complications* / Q000378:metabolism; D002784:Cholesterol / Q000378:metabolism*; D016207:Cytokines / Q000096:biosynthesis*; D006801:Humans; D006949:Hyperlipidemias / Q000150:complications*; D007249:Inflammation / Q000150:complications* / Q000378:metabolism
D016207:Cytokines; D002784:Cholesterol