Oxidized phospholipids modify plasminogen and apolipoprotein(a): Implications for vascular disease

DOI: 10.4236/ajmb.2012.22012   PDF   HTML     3,548 Downloads   7,260 Views  


Whereas the close structural homology between human plasminogen and apolipoprotein(a) has been known for a number of years only recent studies have revealed that both proteins carry linked oxidized phospholipids that may modify the function of these proteins. Future studies should provide a better understanding of oxidized phospholipid adducts and the role played by lipoprotein-associated phospholipase A2 for which cleavage specificity has been established when these modified lipids are in a free form.

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Scanu, A. , Stafforini, D. and Edelstein, C. (2012) Oxidized phospholipids modify plasminogen and apolipoprotein(a): Implications for vascular disease. American Journal of Molecular Biology, 2, 110-112. doi: 10.4236/ajmb.2012.22012.

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The authors declare no conflicts of interest.


[1] McLean, J.W., Tomlinson, J.E., Kuang, W., Eaton, D.L., Chen, E.Y., Fless, G.M., Scanu, A.M. and Lawn, R.M. (1987) cDNA sequence of human apolipoprotein(a) is homologous to plasminogen. Nature, 330, 132-137. doi:10.1038/330132a0
[2] Scanu, A.M. and Fless, G.M. (1990) Lipoprotein(a): Heterogeneity and biological relevance. Journal of Clinical Investigation, 85, 1709-1715. doi:10.1172/JCI114625
[3] Hobbs, H.H. and White, A.L. (1999) Lipoprotein(a): Intrigues and insights. Current Opinion in Lipidology, 10, 225-236. doi:10.1097/00041433-199906000-00005
[4] Scanu, A.M. (1992) Lipoprotein(a)—Its inheritance and molecular basis of its atherothrombotic role. Molecular and Cellular Biochemistry, 113, 127-131. doi:10.1007/BF00231532
[5] Scanu, A.M. (2003) Lipoprotein(a) and the atherothrombotic process: Mechanistic insights and clinical implications. Current Atherosclerosis Reports, 5, 106-113. doi:10.1007/s11883-003-0081-3
[6] Tsimikas, S. and Witztum, J.L. (2008) The role of oxidized phospholipids in mediating lipoprotein(a) atherogenicity. Current Opinion in Lipidology, 19, 369-377. doi:10.1097/MOL.0b013e328308b622
[7] Philips, B. and Scanu, A.M. (2008) Viewing the cardiovascular pathogenicity of Lp(a) from the pro-inflammatory side. Vascular Disease Prevention, 5, 150-155.
[8] Berliner, J.A., Leitinger, N. and Tsimikas, S. (2009) The role of oxidized phospholipids in atherosclerosis. Journal of Lipid Research, 50, S207-S212. doi:10.1194/jlr.R800074-JLR200
[9] Edelstein, C., Pfaffinger, D., Hinman, J., Miller, E., Lipkind, G., Tsimikas, S., Bergmark, C., Getz, G.S., Witztum, J.L. and Scanu, A.M. (2003) Lysine-phosphatidylcholine adducts in kringle V impart unique immunological and potential pro-inflammatory properties to human apolipoprotein(a). Journal of Biological Chemistry, 26, 52841-528447. doi:10.1074/jbc.M310425200
[10] Plow, E.F. and Hoover-Plow, J. (2004) The functions of plasminogen in cardiovascular disease. Trends in Cardiovascular Medicine, 14, 180-186. doi:10.1016/j.tcm.2004.04.001
[11] Edelstein, C., Pfaffinger, D., Yang, M., Hill, J.S. and Scanu, A.M. (2010) Naturally occurring human plasminogen, like genetically related apolipoprotein(a), contains oxidized phosphatidylcholine adducts. Biochimica et Biophysica Acta, 1801, 738-745.
[12] Edelstein, C., Pfaffinger, D., Reichert, E.C., Stafforini, D.M. and Scanu, A.M. (2010) Mouse plasminogen has oxidized phosphatidylcholine adducts that are not metabolized by lipoprotein-associated phospholipase A2 under basal conditions. International Journal of Molecular Science, 11, 5339-5347.
[13] Edelstein, C., Philips, B., Pfaffinger, D. and Scanu, A.M. (2009) The oxidized phospholipids linked to human apolipoprotein(a) do not derive from circulating lowdensity lipoproteins and are probably of cellular origin. FASEB Journal, 23, 950-956. doi:10.1096/fj.08-122002
[14] Tomlinson, J., McLean, J. and Lawn, R. (1989) Rhesus monkey apolipoprotein(a). Journal of Biological Chemistry, 264, 5957-5965.
[15] Stafforini, D.M. (2009) Biology of platelet-activating factor acetylhydrolase (PAF-AH), lipoprotein associated phospholipase A2. Cardiovascular Drugs Therapeutics, 23, 73-83. doi:10.1007/s10557-008-6133-8
[16] Hu, M.M., Zhang, J., Wang, W.Y., Wu, Y.L., Ma, W.H. and Chen, W.P. (2011) The inhibition of lipoprotein-associated phos-pho-lipase A2 exerts beneficial effects against athero-sclerosis in LDLR-deficient mice. Acta Pharmacologica Sinica, 32, 1253-1258.
[17] Wang, W.Y., Zhang, J., Wu, W.Y., Li, J., Ma, Y.L., Chen, W.H., Yan, H., Wang, K., Xu, W.W., Shen, J.H. and Wang, Y.P. (2011) Inhibition of lipoprotein-associated phospholipase A2 ameliorates inflammation and decreases atherosclerotic plaque formation in apoE-defocient mice. PLoS One, 6, e234-e235.
[18] Vladykovskaya, E., Ozhegov, E., Hoetker, J.D., Xie, Z., Ahmed, Y., Suttles, J., Srivastava, S., Bhatnagar, A. and Barski, O.A. (2011) Reductive metabolism increases the proinflammatory activity of aldehyde phospholipids. Journal of Lipid Research, 52, 2209-2225. doi:10.1194/jlr.M013854

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