Apolipoprotein deficiency

Several oxysterol classes present in oxLDL appear to be cytotoxic toward fibroblasts, ECs, and vascular smooth muscle cells, especially 7-hydroperoxycholes-terol (7-OOH-chol), 7P- and 7a-hydroxycholesterol (7-OH-chol), 7-ketocholesterol (7-keto-chol), and cholesterol epoxides (epoxy-chol). 7p-OOH-chol, a precursor of hydroxyl- and keto-oxysterols, was reported to be the most toxic. During LDL oxidation 7P-OOH-chol was produced in three to five times higher quantities than 7a-OOH-chol, other oxysterols and even hydroxy-nonenal, which is one of the most abundant lipid oxidation products. Cytotoxicity of oxysterols was connected to increased cellular oxidative stress. Some studies suggest that oxysterols are even involved in oxidative stress induction. Animal models indicate that dietary oxysterols can significantly decrease glutathione levels and increase expression of glutathione peroxidase and superoxide dismutase. In apolipoprotein-deficient mice, the NADPH-oxidase activity was induced by 7-keto-chol, 7p-OH-chol, and Sp,6P-epoxy-chol. The increased activity of NADPH oxidase yields more superoxide anions that amplify oxidative stress. 

HAYEK T, FURHMAN B, VAYA J, ROSENBLAT M, BELINRY P, COLEMAN R, ELIS A, AVIRAM M (1997) Reduced progression of atherosclerosis in apolipoprotein E-deficient mice following consiunption of red wine, or its polyphenols quercetin or catechin, is associated with reduced susceptibility of LDL to oxidation aggregation, Arteriosclerosis, Thrombosis and Vascular Biology, 17, 2744-52. 

Bea F, Blessing E, Shelley MI, Shultz JM, Rosenfeld ME. Simvastatin inhibits expression of tissue factor in advanced atherosclerotic lesions of apolipoprotein E deficient mice independently of lipid lowering potential role of simvastatin-mediated inhibition of Egr-1 expression and activation. Atherosclerosis 2003 167(2) 187-194. 

Meir KS, Leitersdorf E. Atherosclerosis in the apolipoprotein E-deficient mouse—a decade of progress. Arterioscler Thromb Vase Biol 2004 24(6) 1006-1014. 

Seo HS, Lombardi DM, Polinsky P, et al. Peripheral vascular stenosis in apolipoprotein E-deficient mice—potential roles of lipid deposition, medial atrophy, and adventitial inflammation. Arterioscler Thromb Vase Biol 1997 17(12) 3593—3601. 

Aiello RJ, Bourassa PA, Lindsey S, et al. Monocyte chemoattractant protein-1 accelerates atherosclerosis in apolipoprotein E-deficient mice. Arterioscler Thromb Vase Biol 1999 19(6) 1518-1525. 

Gosling J, Slaymaker S, Gu L, et al. MCP-1 deficiency reduces susceptibility to atherosclerosis in mice that overexpress human apolipoprotein B. J Clin Invest 1999 103(6) 773-778. 

Dawson TC, Kuziel WA, Osahar TA, Maeda N. Absence of CC chemokine receptor-2 reduces atherosclerosis in apolipoprotein E-deficient mice. Atherosclerosis 1999 143(1) 205—211. 

Apolipoprotein AI (apoAI) is the major apolipoprotein of HDL and plays an important role in the formation of mature HDL and the reverse cholesterol transport. HDL concentrations are largely determined by the rate of synthesis of apoAI in the liver. As a consequence deficiency of apoAI results in an almost complete absence of HDL and in accelerated atherosclerosis. In the promoter of the apoAI... 

Diagnosis of lipoprotein lipase deficiency is based on low or absent enzyme activity with normal human plasma or apolipoprotein C-II, a cofactor of the enzyme. 

Tangirala RK, Rubin EM, Palinski W (1995) Quantitation of atherosclerosis in murine models correlation between lesions in the aortic origin and in the entire aorta, and differences in the extent of lesions between sexes in LDL receptor-deficient and apolipoprotein E-deficient mice. J Lipid Res 36 2320-2328... 

Apochromatic objectives, 16 471 Apocynaceae, alkaloids in, 2 75 Apodization process, 14 227 apo E gene, and LDL level, 5 136 Apoglucose oxidase (apo-GOD), 14 148 Apolipoprotein B deficiencies, 17 652 Apparel, nylon, 19 766 Apparent bypass... 

Hirsch-Reinshagen, V., Zhou, S., Burgess, B.L., et al. (2004) Deficiency of ABCAl impairs apolipoprotein A metabolism in brain. J. Biol. Chem., 279, 41197-41207. 

Athanasopoulos, T., Owen, J.S., Hassall, D.G., et al. (2000) Intramuscular injection of a plasmid vector expressing human apolipoprotein E hmits progression of xanthoma and aortic atheroma in apoE-deficient mice. Hum. Mol. Genet., 9, 2545-2551. 

Harris, J.D., Graham, I.R., Schepelmann, S., et al. (2002) Acute regression of advanced and retardation of early aortic atheroma in immunocompetent apolipoprotein-E (apoE) deficient mice by administration of a second generation (E1-, E3-, polymerase-) adenovirus vector expressing human apoE. Hum. Mol. Genet., 11, 43-58. 

McLachlan, C.S., Yi Xing Soh, C. (2005) Differences in anxiety-related behaviour between apolipoprotein E-deficient C57BL/6 and wild type C57BL/6 mice. Physiol. Res., 54, 701-704. 

Funke H, Eckardstein A von, Pritchard PH, Karas M, Albers JJ, Assmann G (1991) A frame-shift mutation in the human apolipoprotein A-I gene causes high density lipoprotein deficiency, partial lecithin cholesterol-acyltransferase deficiency, and corneal opacities. J Clin Invest 87 371-376... 

Ng DS, Leiter LA, Vezina C, Connelly PW, Hegele RA (1994) Apolipoprotein A-I Q[-2]X causing isolated apolipoprotein A-I deficiency in a family with analphalipoproteinemia. J Clin Invest 93 223-229... 

Production of LDL from VLDL in the plasma With these modifications, the VLDL is converted in the plasma to LDL. An intermediate-sized particle, the intermediate-density lipoprotein (IDL) or VLDL remnant, is observed during this transition. IDLs can also be taken up by cells through receptor-mediated endocytosis that uses apo E as the ligand. [Note Apolipoprotein E is normally present in three isoforms, E2, E3, and E4. Apo E2 binds poorly to receptors, and patients who are homozygotic for apo E2 are deficient in the clearance of chylomicron remants and IDLs. The individuals have familial type III hyperlipoproteinemia (familial dysbetalipoproteinemia, or broad beta disease), with hypercholesterolemia and premature atherosclerosis. Not yet understood is the fact that the E4 isoform confers increased susceptibility to late-onset Alzheimer disease.]... 

Moulton, K.S., Heller, E., Konerding, M.A., Flynn, E., Palinski, W. and Folkman, J. (1999) Angiogenesis inhibitors endostatin or TNP-470 reduce intimai neovascularization and plaque growth in apolipoprotein E-deficient mice. Circulation, 99, 1726-1732. 

Aviram, M. et al., Pomegranate juice consumption reduces oxidative stress, atherogenic modifications to LDL, and platelet aggregation studies in humans and in atherosclerotic apolipoprotein E-deficient mice. Am. J. Clin. Nutr., 71, 1062-1076, 2000. 

All these antioxidative and anti-atherogenic effects of pomegranate polyphenols were clearly demonstrated in vitro, as well as in vivo in humans, and in the atherosclerotic apolipoprotein E-deficient mice. Dietary supplementation of pomegranate juice rich in polyphenols to patients with severe carotid artery stenosis or to atherosclerotic mice resulted in a significant inhibition in the development of the... 

Fuhrman, B. et al., Grape powder polyphenols attenuate atherosclerosis development in apolipoprotein E-deficient (E°) mice and reduce macrophage atherogenicity, J. Nutr., 135, 722, 2005. 

Rosenblat M., Volkova N., Coleman R., and Aviram M., Pomegranate by-product administration to apolipoprotein E-deficient mice attenuates atherosclerosis development as a result of decreased macrophage oxidative stress and reduced cellular uptake of oxidized low-density lipoprotein, J. Agric. Food. Chem., 54, 1928, 2006. 

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