Oxidized lipoproteins

BERLINER J A and HEINECKE J w (1996) The role of oxidized lipoproteins in atherosclerosis Free Radical Biology and Medicine 20, 707-27. 

There is a long-standing hypothesis that the microvasculature plays a pathological role in forms of chronic inflammatory polyarthritis, particularly RA (Rothschild and Masi, 1982). One of the proposed mechanisms of vascular damage in connective tissue disease is the direct action of a cytotoxic serum factor inducing endothelial cell damage. Blake et al. (1985) have su ested that the vascular abnormalities associated with RA may be linked to oxidized lipoproteins because they are cytotoxic to endothelial cells. 

Andalibi, A., Liao, F., Imes, S., Fogelman, A.M. and Lusis, A.J. (1993). Oxidized lipoproteins influence gene expression by causing oxidative stress and activating the transcription factor NF-xB. Biochem. Soc. Trans. 21, 651-655. 

Chin, J.H., Azhar, S. and Hoffman, B.B. (1992). Inactivation of endothelial derived relaxing factor by oxidized lipoproteins. 

Fig. 2. The role of MCP-1 (CCL2)/CCR2 in atherosclerosis is thought to occur through the response of endothelial cells and vascular smooth muscle cells to oxidized lipoproteins. After injury by oxidized lipoproteins, MCP-1 is released and attracts CCR2-expressing monocytes to the site of injury and activates them to secrete inflammatory mediators.

Minami M, Kume N, Shimaoka T, et al. Expression of scavenger receptor for phosphatidylserine and oxidized lipoprotein (SR-PSOX) in human atheroma. Ann N Y Acad Sci 2001 947 373-376. 

Berliner, J.A., and Heinecke, J.W., 1996a, The role of oxidized lipoproteins in atherogenesis. Free Radic. Biol. Med. 20 707-27. 

Hajjar, D.P., 2000, Oxidized lipoproteins and infectious agents. Are they in collusion to accelerate atherogenesis , Arieriosc/er. Thromb. Vase. Biol. 20 1421-1422. 

Role of oxidized lipoproteins in plaque formation in arterial wall. 

As mentioned in Chapter 21, there are several related receptors with similar structures. Two of them have a specificity for apolipoprotein E and can accept remnants of VLDL particles and chylomicrons.216 220 The LDL receptor-related protein is a longer-chain receptor.216 221 LDL particles, especially when present in excess or when they contain oxidized lipoproteins, may be taken up by endocytosis into macrophages with the aid of the quite different scavenger receptors.221 225 The uptake of oxidized lipoproteins by these receptors may be a major factor in promoting development of atherosclerosis (Box 22-B). On the other hand, scavenger receptor SR-B1, which is also present in liver cells, was recently identified as the receptor for HDL and essential to the "reverse cholesterol transport" that removes excess cholesterol for excretion in the bile.213/213a... 

There might be another crucial point as far as oxidized LDL is concerned. The presence of oxidized lipids in the gut allows the formation of oxidized chilomicrons followed by the production in the liver of oxidized lipoproteins. Once they are formed, vitamin E may reduce the propagation of the oxidation and becomes an a-tocopheryl radical (the major oxidation product of vitamin E), Once this radical is present at high concentration it is capable of oxidizing the apolipoprotein moiety of the LDL (32,33),... 

Macrophages consume excess modified (oxidized) lipoprotein, becoming foam cells. 

Pawlowicz, P, Wilczynski, J., Stachowiak, G., and Hincz, P, Administration of natural anthocyanins derived from chokeberry retardation of idiopathic and preeclamptic origin. Influence on metabobsm of plasma oxidized lipoproteins the role of autoantibodies to oxidized low density bpoproteins, Ginekol. Polska, 71, 848-853, 2000. 

Beaudeux, J., Cesarini, ML, Gardes-Albert, M, Maclouf, J, Merval, R, Esposito, B, Peynet, J, and Tedgui, A (1997). Native and gamma radiolysis-oxidized lipoprotein(a) increase the adhesiveness of rabbit aortic endothelium. Atherosclerosis 132(1) 29-35. 

Jessup W. 1996. Oxidized lipoproteins and nitric oxide. Curr. Opin. Lipidol. 7 274-80... 

I am especially indebted to Fabrice Collin for his talented designs of lipid aggregates and molecular mechanisms and for his judicious comments. I would like to acknowledge Prof. Dominique Bonnefont-Rousselot for her precious collaboration all along the story of oxidized lipoproteins (EA 3617, Faculty de Pharmacie, Universite Paris 5). 

SR-PSOX Scavenger receptor for phosphatidylserine and oxidized lipoprotein... 

Itabe H, Takeshima E, Iwasaki H, et al. (1994) A monoclonal antibody against oxidized lipoprotein recognizes foam cells in atherosclerotic lesions. Complex formation of oxidized phosphatidylcholines and polypeptides. J Biol Chem 269 15274-15279... 

Jessup W, Wilson P, Gaus K, et al. (2002) Oxidized lipoproteins and macrophages. Vascul Pharmacol 38 239— 248... 

Hartwich, J. et al. Regulation of platelet adhesion by oxidized lipoproteins and oxidized phosphohpids. Platelets. 13(May 2002) 141-51. 

Palinski, W. et al. Cloning of monoclonal autoantibodies to epitopes of oxidized lipoproteins from apohpoprotein E-deflcient mice. Demonstration of epitopes of oxidized low density lipoprotein in human plasma. J. Clin. Invest. 98 (1996) 800-14. 

In recent years most studies on oxidized phospholipids have been performed using mixtures of oxidation products that are generated from their polyunsaturated parent compounds like PA-PC or oxidized lipoprotein particles (e.g. oxLDL). These preparations contain a large variety of different substances differing in structure, polarity and hydrophobicity as well as bioavailability. In many of these oxidized lipid preparations, neither the type nor the content of the individual oxidized components was known. Therefore, the respective compounds contribute to the apparent biological activities of oxidized lipid mixtures to a different and unpredictable extent. Thus, it will be desirable to concentrate on chemically defined lipid species in the future. 

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