Foam cells metabolism

To explain the relationship between Lp(a) concentrations and risk of atherosclerosis, several hypothesis could be brought forward first, Lp(a) affects the metabolism of cholesterol and LDL secondly, Lp(a) plays a role in foam-cell and plaque formation thirdly, Lp(a) interacts with the activation of plasminogen to plasmin, the key step in the fibrinolytic system (L10, M27). Such activation can occur in two different localizations, i.e., on fibrin and its proteolytic residues, and on the surface of endothelial and monocytic cells. 

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],... 

Mucolipidoses are characterized by a combined metabolic disorder of mucopolysaccharides, lipids, and glycoproteins. Lysosomal storage and foamy swollen Kupffer cells with hepatomegaly may be seen. In some of the numerous types, the underlying enzymatic defects have not yet been detected. Type II is also called Leroy syndrome (J.G. Leroy et al., 1967). Due to distinctive cytoplasmic inclusions in fibroblast cultures, this disorder is also known as inclusion cell disease (J.G. Leroy et al., 1971). Foamy altered stellate cells, macrophages and also epithelioid foam cell granulomas are found. 

Abnormal lipoproteins are produced under various metabolic conditions. P-VLDL, a triglyceride-depleted, cholesterol-enriched form of VLDL, accumulates in the plasma of cholesterol-fed animals [13,14] or of humans with type III hyperlipoproteinemia [15]. In patients with this disease, the accumulation of j8-VLDL is believed to be due to incomplete clearance of chylomicron remnants by the liver. Slow turnover of remnants allows them to accumulate cholesteryl esters and thus to evolve into j8-VLDL particles [16,17]. -VLDL (density <1.006 g/ml, j8-electro-phoretic mobility) contain both apo-B and apo-E and may play a significant role in the formation of atherosclerotic foam cells [18]. 

Excess cholesterol can also be metabolized to CE. ACAT is the ER enzyme that catalyzes the esterification of cellular sterols with fatty acids. In vivo, ACAT plays an important physiological role in intestinal absorption of dietary cholesterol, in intestinal and hepatic lipoprotein assembly, in transformation of macrophages into CE laden foam cells, and in control of the cellular free cholesterol pool that serves as substrate for bile acid and steroid hormone formation. ACAT is an allosteric enzyme, thought to be regulated by an ER cholesterol pool that is in equilibrium with the pool that regulates cholesterol biosynthesis. ACAT is activated more effectively by oxysterols than by cholesterol itself, likely due to differences in their solubility. As the fatty acyl donor, ACAT prefers endogenously synthesized, monounsaturated fatty acyl-CoA. 

Ascorbate supplementation prevents the exacerbation of CVD associated with hypertriglyceridemia. Type III hyperlipidemia, and related disorders by stimulating lipoprotein lipases and thereby enabling a normal catabolism of triglyceride-rich lipoproteins." Ascorbate prevents the oxidative modification of these lipoproteins, their uptake by scavenger cells and foam cell formation. Moreover, we propose here that, analogous to the LDL receptor, ascorbate also increases the expression of the receptors involved in the metabolic clearance of triglyceride-rich lipoproteins, such as the chylomicron remnant receptor. 

The role of atherogenic lipoproteins on inflammation has been reviewed in ref. 196. PAF (a proinflammatory phospholipid) metabolism is independent of cellular cholesterol content, and foam cells and macrophages produce transiently PAF upon phagocytosis at inflammatory sites in intima (197). On the other hand, in HUVEC Apo E, secreted locally at lesion sites by macrophages may be anti-inflammatory (198). 

FIGURE 7.4 Hepatic spheroid in structure of polyurethane foam. (From Yamashita, Y. et ah, High Metabolic Function of Primary Human and Porcine Hepatocytes, Cell Transplantation, Vol. 11, pp. 379-384, 2002.)... 

The gradual reduction in cellular activity, culminating in culture death a few days after cultures were stoppered, was clearly the result (directly or indirectly) of changes in dissolved gas concentrations. Otherwise, the cells would have continued actively metabolizing as long as did the conventional unstoppered cultures. The conventional cultures, capped with permeable foam and foil, con-... 

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