Journal of Lipid Research, Vol 38, 2193-2206, Copyright © 1997 by Lipid Research, Inc.

REVIEWS

Learning about the structure and biology of human lipoprotein [a] through dissection by enzymes of the elastase family: facts and speculations

AM Scanu and C Edelstein
Department of Medicine, University of Chicago, Pritzker School of Medicine, IL 60637, USA.

Lipoprotein[a], Lp[a], represents a class of lipoprotein particles that have as a protein moiety apoB-100 linked by a disulfide bridge to a multi-kringle structure, apolipoprotein[a], or apo[a]. It is now possible to separate from Lp[a] a free apo[a] able to reassociate with apoB-100-containing lipoproteins to restore the parent lipoprotein complex. Apo[a], whether free or a constitutive component of Lp[a], can be cleaved at interkringle sites by the action of enzymes of the elastase family generating fragments that differ in structural, functional, and metabolic properties. In the case of Lp[a], elastase digestion generates a miniLp[a] particle, which contains the apo[a] COOH-terminal domain able to bind to lysine, fibrinogen, fibronectin, and proteoglycans. This domain may also be generated by elastase type enzymes secreted by activated macrophages and smooth muscle cells in the arterial intima as a part of the chronic inflammation that characterizes the atherosclerotic process. Thus, the apo[a] immunoreactive material, which has been described in the atherosclerotic plaque, may represent miniLp[a] and/or apo[a] fragments accumulating in the vessel wall as a function of their relative affinity for the components of the extracellular matrix and producing complexes with an atherothrombogenic potential. This potential may depend on several factors: kringle folding and conformation, susceptibility of the linkers to proteolytic cleavage, binding specificity of given apo[a] fragments to the matrix components of the arterial intima, and the overall inflammatory status of the arterial wall.
CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				E. Anuurad, G. Lu, J. Rubin, T. A. Pearson, and L. Berglund ApoE genotype affects allele-specific apo[a] levels for large apo[a] sizes in African Americans: the Harlem-Basset Study J. Lipid Res., March 1, 2007; 48(3): 693 - 698. [Abstract] [Full Text] [PDF]

				C. Edelstein, M. Yousef, and A. M. Scanu Elements in the C terminus of apolipoprotein [a] responsible for the binding to the tenth type III module of human fibronectin J. Lipid Res., December 1, 2005; 46(12): 2673 - 2680. [Abstract] [Full Text] [PDF]

				L. Berglund and R. Ramakrishnan Lipoprotein(a): An Elusive Cardiovascular Risk Factor Arterioscler. Thromb. Vasc. Biol., December 1, 2004; 24(12): 2219 - 2226. [Abstract] [Full Text] [PDF]

				C. Edelstein, D. Pfaffinger, J. Hinman, E. Miller, G. Lipkind, S. Tsimikas, C. Bergmark, G. S. Getz, J. L. Witztum, and A. M. Scanu Lysine-Phosphatidylcholine Adducts in Kringle V Impart Unique Immunological and Potential Pro-inflammatory Properties to Human Apolipoprotein(a) J. Biol. Chem., December 26, 2003; 278(52): 52841 - 52847. [Abstract] [Full Text] [PDF]

				C. Edelstein, S. D. Shapiro, O. Klezovitch, and A. M. Scanu Macrophage Metalloelastase, MMP-12, Cleaves Human Apolipoprotein(a) in the Linker Region between Kringles IV-4 and IV-5. POTENTIAL RELEVANCE TO LIPOPROTEIN(a) BIOLOGY J. Biol. Chem., April 9, 1999; 274(15): 10019 - 10023. [Abstract] [Full Text] [PDF]

				V. Mooser, F. Tinguely, P. Fontana, V. Lenain, M. Vaglio, P. Ruchat, L. K. von Segesser, S. M. Marcovina, M. Markert, R. Darioli, et al. Effect of Cardiopulmonary Bypass and Heparin on Plasma Levels of Lp(a) and Apo(a) Fragments Arterioscler. Thromb. Vasc. Biol., April 1, 1999; 19(4): 1060 - 1065. [Abstract] [Full Text] [PDF]

				F. Nassir, D. K. Bonen, and N. O. Davidson Apolipoprotein(a) Synthesis and Secretion from Hepatoma Cells Is Coupled to Triglyceride Synthesis and Secretion J. Biol. Chem., July 10, 1998; 273(28): 17793 - 17800. [Abstract] [Full Text] [PDF]

				B. Garner, A. H. Merry, L. Royle, D. J. Harvey, P. M. Rudd, and J. Thillet Structural Elucidation of the N- and O-Glycans of Human Apolipoprotein(a). ROLE OF O-GLYCANS IN CONFERRING PROTEASE RESISTANCE J. Biol. Chem., June 15, 2001; 276(25): 22200 - 22208. [Abstract] [Full Text] [PDF]