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By De Jong, Nijman And Roell

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72. 73. 74. 75. 76. 77. 78. 79. 80. 81. 15 Grote K, Flach I, Luchtefeld M, et al Mechanical stretch enhances mRNA expression and proenzyme release of matrix metalloproteinase-2 (MMP-2) via NAD(P)H oxidasederived reactive oxygen species. Circ Res 2003;92:e80-6. Ceriello A, Motz E. Is Oxidative stress the pathogenic mechanism underlying insulin resistance, diabetes, and cardiovascular disease? The common soil hypothesis revisited. Arterioscler Thromb Vase Biol 2004;24:816-23. Blendea MC, Jacobs D, Stump CS, et al.

J Clin Invest 1999;104:135-6. Gaut JP, Byun J, Tran HD et al. Myeloperoxidase produces nitrating oxidants in vivo. J Clin Invest 2002;109:1311-9. Daugherty A, Dunn JL, Rateri DL et al. Myeloperoxidase, a catalyst for lipoprotein oxidation, is expressed in human atherosclerotic lesions. J Clin Invest 1994;94:437-44. Brennan ML, Penn MS, Van Lente F et al. Prognostic value of myeloperoxidase in patients with chest pain. N Engl J Med 2003;349:1595-604. Brennan ML, Anderson MM, Shih DM et al. Increased atherosclerosis in myeloperoxidase-deficient mice.

Unlike the LDL receptor which downregulates as the cell cholesterol content increases, the acetyl LDL receptor, which is expressed at normal levels in patients with LDLR deficiency, is not downregulated and is fully active even as the cell cholesterol content increases markedly. Kodama et al^^^^ subsequently cloned and sequenced the acetyl LDL receptor which was redesignated the scavenger receptor, type A, or SR-A. In vitro, chemical acetoacetylation or conjugation of LDL with malondialdehyde (MDA) or via aggregated platelets releasing MDA generates MDA-LDL, which is recognized by SR-A^^^'^^\ However, the concentrations of MDA needed to generate MDA-LDL in vitro seem to be significantly higher than could be achieved in vivo, although MDA-LDL epitopes are abundant in atherosclerotic lesions^^^"^^^ Lipoproteins and oxidation Ti Endothelial cells, smooth muscle cells or macrophages Native LDL > Acetyl LDL V oxLDL 1 i Slow \ Native LDLR (downregulated) Acetyl LDLR ^ SR-A (not downregulated) CD36.

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