Learning about the structure and biology of human lipoprotein [a] through dissection by enzymes of the elastase family: facts and speculations.
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.
Scanu
A M
AM
Department of Medicine, University of Chicago, Pritzker School of Medicine, IL 60637, USA.
Edelstein
C
C
D000595:Amino Acid Sequence; D053299:Apolipoprotein B-100; D001054:Apolipoproteins A / Q000737:chemistry; D001055:Apolipoproteins B / Q000737:chemistry; D002240:Carbohydrate Sequence; D004220:Disulfides / Q000737:chemistry; D006801:Humans; D018082:Kringles; D019272:Leukocyte Elastase / Q000378:metabolism; D017270:Lipoprotein(a) / Q000737:chemistry* / Q000378:metabolism*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010196:Pancreatic Elastase / Q000378:metabolism*; D010446:Peptide Fragments / Q000737:chemistry; D011487:Protein Conformation
D053299:Apolipoprotein B-100; D001054:Apolipoproteins A; D001055:Apolipoproteins B; D004220:Disulfides; D017270:Lipoprotein(a); D010446:Peptide Fragments; D010196:Pancreatic Elastase; D019272:Leukocyte Elastase