Foam cells transport

Macrophage/athero- t Reverse cholesterol transport from foam cells l Progression of atherosclerosis... 

Binding of Lp(a) to fibronectin, a connective tissue component in atherosclerotic plaques, when considered in adjunct to the former observations, supports the hypothesis that Lp(a), just like LDL, is transported through endothelium, and subsequently immobilized in the arterial intima by binding of matrix components (V6a). The particle then possibly undergoes oxidative modification, is taken up by macrophages, and therefore contributes to foam cell formation and atherogenesis (SI). 

Low HDL cholesterol (<35 mg/dL) is an independent risk factor for CHD. HDL appears to antagonize atherogenesis by at least two mechanisms. HDL can mobilize cholesterol from extrahepatic cells (such as arterial wall foam cells) and transport it to the liver for disposal (reverse cholesterol transport) HDL also has antioxidant properties. HDL contains the potent antioxidant enzyme paraoxonase, which may protect LDL lipids from oxidation. Thus, hypertriglyceridemia with... 

However, as cell growth proceeds, the physical as well as chemical constraints of the triblock terpolymers inhibit pronounced growth within the PB phase. Instead, the nucleated cells tend to grow into the SAN/PMMA phase. As the PPE/PS phase still stores a significant amount of carbon dioxide, the blowing agent is subsequently transported along the interface towards the foam cells. Apparently the PPE/PS phase still acts similar to a solid phase. 

Sterol carrier protein 2 has also been shown to be involved in the intracellular transport and metabolism of cholesterol. Hirai et al. (1994) suggested that sterol carrier protein 2 plays an important role during foam cell formation induced by acetylated LDL and may be an important step in atherosclerosis [142], Lipoproteins can bind lipopolysaccharide and decrease the lipopoly-saccharide-stimulated production of proinflammatory cytokines [142, 143], In addition, lipoprotein entrapment by the extracellular matrix can lead to the progressive oxidation of LDL because of the action of lipoxygenases, reactive oxygen species, peroxynitrite, or myeloperoxidase [144, 145],... 

Vainio S, Ikonen E. Macrophage cholesterol transport A critical player in foam cell formation. Ann Med 2003 35 146-155. 

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). 

The initial steps of reverse cholesterol transport involve export of cholesterol from peripheral cells to plasma lipoproteins for subsequent delivery to the liver. In vivo, HDL or its apolipoproteins act as acceptors of cholesterol from peripheral cells, carrying it to the liver for degradation. When cholesterol acceptors such as HDL are present, cholesterol efflux from macrophages is accelerated, which prevents foam cell formation. To produce this efflux, neutral cholesteryl ester hydrolase catalyzes intracellular hydrolysis of cholesteryl esters into free cholesterol in the lysosome (Avart et al. 1999). 

A comparison of the United States with other countries shows similar relationships between total cholesterol and LDL and an inverse relationship with HDL and coronary artery disease (CAD) mortality. On a positive note, the U.S. mortality rate is midway among the countries studied, and this country has had the greatest decline in CAD mortality (35% to 40%) in men and women over the last 10 years compared with other countries. A decline in the prevalence of hypercholester-olemiain certain segments of the U.S. population parallels these trends in mortality. LDL and the ratio of LDL to HDL also have been used to assess risk, but their use adds little information to total cholesterol alone unless HDL is abnormally high or low. HDL transports cholesterol from lipid-laden foam cells to the liver. HDL has been shown to be protective for the occurrence of CHD, and an inverse relationship exists between CHD and HDL levels. ... 

In addition to Its role In atheroprotective reverse cholesterol transport, HDL Itself and some plasma enzymes associated with HDL can suppress the oxidation of LDL. Decreased LDL oxidation presumably reduces the substrates for scavenger receptors on macrophages, thereby Inhibiting their accumulation of LDL cholesterol and thus foam cell formation. HDL also appears to have anti-inflammatory properties, which may contribute to Its atheroprotective effect. Finally, the interaction of HDL with the receptor SR-BI can stimulate the activity of endothelial nitric oxide (NO) synthase, leading to increased production of nitric oxide. 

ACAT or a decrease in ACAT activity itself. Because much of the cholesterol accumulating in the cells appears to be associated with lysosomes, it is tempting to speculate that defects in lysosomal cholesterol transport arise in advanced foam cells. In this context, macrophages exposed to oxidized LDL can internalize a substantial amount of cholesterol, but there is relatively little stimulation of ACAT-mediated cholesterol esterification [8]. According to one model, oxysterol-induced inhibition of lysosomal sphingomyelinase leads to accumulation of lysosomal sphingomyelin, which binds cholesterol and thus inhibits transport of the cholesterol out of lysosomes (M. Aviram, 1995). 

LDLs are lipoprotein complexes referred to as "bad cholesterol" because prolonged elevation of LDL levels leads to atherosclerosis. LDLs are the primary transport vehicle for cholesterol synthesized in the liver (See Figure 18.7). Oxidation of LDLs leads to foam cell formation and ultimately an atherosclerotic plaque. The primary apoprotein contained in LDLs is Apo B-100. 

Low-density lipoprotein complexes (LDLs), which are the primary means of transporting cholesterol in the blood, are readily oxidized. These oxidations include peroxidation of unsaturated fatty acids, hydroxylation of cholesterol, and oxidation of amino acid residues in the apoprotein. A class of white blood cells recognizes the oxidation and absorbs the LDL through its scavenger receptor. After a white blood cell has absorbed numerous LDLs containing cholesterol, it becomes engorged and is referred to as a foam cell. Foam cells attract other white blood cells, which leads to accumulation of more cholesterol. Ultimately, this accumulation of cholesterol becomes one of the chief chemical constituents of the atherosclerotic plaque that forms at the site. 

A major benefit of HDL particles derives from their ability to remove cholesterol from cholesterol-laden cells and to return the cholesterol to the liver, a process known as reverse cholesterol transport. This is particularly beneficial in vascular tissue by reducing cellular cholesterol levels in the subintimal space, the likelihood that foam cells (lipid-laden macrophages that engulf oxidized LDL-cholesterol and represent an early stage in the development of atherosclerotic plaque) will form within the blood vessel wall is reduced. 

LDL is one of the major carriers of cholesterol in circulation. LDL is also known as a bad lipoprotein due to the fact that LDL transports cholesterol and other fat molecules to peripheral tissues (i.e. arterial walls) and plays a crucial role in the development of several cardiovascular-related diseases such as atherosclerosis, stroke, and myoeardial infarction. Oleic acid and lysophosphatidylcholine (Figure 5) are the major constituents of LDL. Oxidized LDL (ox-LDL) is rapidly engulfed by macrophages to induce foam cell formation in the arterial wall [37]. Therefore, ox-LDL is thought to be one of the major contributors to the development of atherosclerosis. Moreover, ox-LDL can enhance coronary vasospasm (vasoconstriction) via induce endotheliinn-dependent vasoconstriction consequently preventing vasodilation and increase the activity of protein kinase C isoforms a and 8 in VSMCs of porcine coronary arteries [38-40]. 

PPARs enhance cholesterol efflux and stimulate critical steps of the reverse cholesterol transport pathway (reviewed in ref. 507). PUFA and activating PPAR increase hepatic cholesterol uptake. PPARy induces expression of SR B1 in rat hepatocytes, liver EC, and Kuppfer cells (508). PPARa activation in human macrophages and foam cells results in an enhanced availability of free cholesterol for efflux through the ABCAl pathway by reducing cholesterol esterification rates and ACATl activity (509). 

The occurrence in the liquor of foam cells measuring from 20—40 [x has been described by Tourtelotte et al. (1965). They are similar to those which may occasionally be found in normal subjects, and their identity with lipomacrophages and a possible role in lipid transport via the Virchow-Robin spaces into the liquor has been discussed, since their number was correlated with abnormalities in the lipid profile of the liquor. 

Some of the key factors that lead us to select polyurethane foam for upholstery are its durability, resilience, and controllable hardness (or softness, depending on your point of view). Vibration dampening and shock absorbance are important attributes in automobile and public transportation seating. Open cell foams are preferred for these applications because they allow for air and moisture transport, which improve the comfort of passengers who may occupy a seat continuously for several hours. This inherent breathability is also a valuable attribute in mattresses. Shock absorbance plays a key role in selecting flexible polyurethane foams for the packaging of fragile items. 

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