Macrophage foam cells

KAPLAN M and AVIRAM M (1999) Oxidized low density lipoprotein atherogenic and proinflammatoiy characteristics during macrophage foam cell formation. An inhibitory role for nutritional antioxidants and serum paraoxonase Clinical Chemistry Laboratory Medicine 37,111-9,1. 

Brown, M. S. and Goldstein, J.L. (1980). The cholesteryl ester cycle in macrophage foam cells. J. Biol. Chem. 255, 9344-9352. 

Wang N, Tabas I, Winchester R, Ravalli S, Rabbani LE, Tall A. Interleukin 8 is induced by cholesterol loading of macrophages and expressed by macrophage foam cells in human atheroma. J Biol Chem 1996 271(15) 8837-8842. 

Chinetti G, Lestavel S, Bocher V, Re-maley AT, Neve B, Torra IP, et al. PPAR-alpha and PPAR-gamma activators induce cholesterol removal from human macrophage foam cells through stimulation of the ABCA1 pathway. Nature Med 2001 7 53-58. 

At autopsy, a ruptured plaque features a thin fibrous cap overlying cell-rich regions with a lipid-rich necrotic core (<3 mm ) containing cell debris. The indicators for plaque instability include an inflammatory infiltrate with lipid-rich macrophages (foam-cells) and a decreased collagen and smooth muscle cell (SMC) content in the fibrous caps as well as at the shoulders of the atheroma, respectively. Therefore, one of the challenges of modern medicine is the design of... 

The atherosclerotic lesions develop in a complex, chronic process. The first detectable lesion is the so-called fatty streak, an aggregation of lipid-laden macrophage foam cells. The next stage of development is the formation of plaques consisting of a core of lipid and necrotic cell debris covered by a layer of connective tissue and smooth muscle cells. These plaques hinder arterial blood flow and may precipitate clinical events by plaque rupture and thrombus formation. Platelets from the thrombi, activated macrophages, and smooth muscle cells release growth factors and cytokines resulting in an inflammatory-fibroproliferative response that leads to the advanced lesions of atherosclerosis. 

Kalayoglu, M.V., and Byrne, G.I., 1998a, A Chlamydia pneumoniae component that induces macrophage foam cell formation is chlamydial hpopolysaccharide, Infect. Immun. 66 5067-5072. 

Kalayoglu, M.V., Byme, G.I., 1998b, Induction of macrophage foam cell formation by Chlamydia pneumoniae,/. Infect. Dis. 177 725-729. 

The oxysterol 7-ketocholesterol is an important COP involved in atherosclerotic lesions and macrophage foam cells (275). There is no direct evidence in humans that COPs contribute to atherogenesis, but it has been found that COP levels are elevated in LDL subfractions that are considered potentially atherogenic (276). In addition, raised levels of 7p-hydroxycholesterol may be associated with an increased risk of atherosclerosis. Arterial injury by COPs causes endothelial dysfunction and arterial wall cholesterol accumulation (277). Even under normocholesterolemic conditions, COPs can cause endothelial dysfunction, increased macromolecular permeability, and increased cholesterol accumulation. These are all factors believed to be involved in the development of atherosclerotic lesions. The atherogenic potential of COPs has been demonstrated by in vitro cell culture (73, 278), as well as in animal feeding studies (279). Japanese quail fed either purified cholesterol or oxidized cholesterol exhibited greater plasma and liver cholesterol concentrations in association with increased severity of atherosclerotic lesions when fed the oxidized cholesterol (279). 

Interventions that block oxidative modification of LDL are currently under intensive study [1,3-5,10]. If oxidative modification of LDL results in enhanced uptake by macrophages, use of an appropriate antioxidant should protect LDL from oxidation, decrease the rate of LDL uptake by macrophage foam cells and slow the development of fatty streaks in the arterial wall. The role of antioxidants in preventing oxidative modification of LDL has been evaluated in a number of studies [1,5,8,10]. In our investigation we studied the influence of the vitamin E reach diet on the copper-mediated oxidizability of plasma LDL from patients with atherosclerosis. So far as LDL is the main transport form of natural antioxidant a-tocopherol we were surprised to find that during 3-months vitamin E supplementation in the daily dose 400 mg the oxidation resistance of LDL did not increase (Figure 14). 

Galis ZS, Sukhova GK, Kranzhofer R, Clark S, Libby P (1995) Macrophage foam cells from experimental atheroma constitutively produce matrix-degrading proteinases. Proc Natl Acad Sci U S A 92 402-406... 

The efflux process for the removal of lipids from macrophage foam cells is critical for the... 

Gelissen 1C, Brown AJ, Mander EL, et al. (1996) Sterol efflux is impaired from macrophage foam cells selectively enriched with 7-ketocholesterol. J Biol Chem 271 17852-17860... 

Gelissen 1C, Rye KA, Brown AJ, et al. (1999) Oxysterol efflux from macrophage foam cells the essential role of acceptor phospholipid. J Lipid Res 40 1636-1646... 

Ob). As macrophage foam cells accumulate in an artery wall, they initially form an early fatty streak, the first unique step in atherosclerosis (Figure 18-19b). 

As noted, the first unique step of atherosclerosis is the accumulation in the artery wall of macrophage foam cells filled with lipid droplets containing cholesteryl esters. The greater the plasma LDL concentration and the greater the concentration of LDL in the artery wall, the more rapidly foam cells... 

Normal Inflammatory responses in an artery wall, triggered by infection or Injury, may lead to the formation and accumulation of cholesterol-filled macrophage foam cells, the first indication of atherosclerosis. 

Podrez, E.A. et al. A novel family of atherogenic oxidized phospholipids promotes macrophage foam cell formation via the scavenger receptor CD36 and is enriched in atherosclerotic lesions 1. J. Biol. Chem. 277 (2002a) 38517-23. 

Marathe, S., Choi, Y., Leventhal, A.R., and Tabas, I., Sphingomyelinase converts lipoproteins from apolipoprotein E knockout mice into potent inducers of macrophage foam cell formation, Arterioscler Thromb Vase Biol, 20 (2000) 2607-2613. 

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