Atherothrombogenicity of lipoprotein(a): the debate.
Although lipoprotein(a) (Lp[a]) has been recognized as an atherothrombogenic factor, the underlying mechanisms for this pathogenicity have not been clearly defined. Plasma levels have received most of the attention in this regard; however, discrepancies among population studies have surfaced. Particularly limited is the information on the fate of Lp(a) that enters the arterial wall, in terms of mechanisms of endothelial transport and interactions with cells and macromolecules of the extracellular matrix. A typical Lp(a) represents a low-density lipoprotein (LDL)-like particle having as a protein moiety apo B-100 linked by a single interchain disulfide bond to a unique multikringle glycoprotein, called apolipoprotein(a) (apo[a]). In vitro studies have shown that Lp(a) can be dissected into its constituents, LDL and apo(a). In turn, the latter can be cleaved by enzymes of the elastase and metalloproteinase families into fragments that exhibit a differential behavior in terms of binding to macromolecules of the extracellular matrix: fibrinogen, fibronectin, and proteoglycans. By immunochemical criteria, apo(a) predominantly localizes in areas of human arteries affected by the atherosclerotic process, where elastase and metalloproteinase enzymes operate and where apo(a) fragments are potentially generated. The accumulation of these fragments in the vessel wall is likely to depend on their affinity for the constituents of the extracellular matrix. Thus, factors that modulate inflammation and inflammation-mediated fragmentation of Lp(a)/apo(a) may play an important role in the cardiovascular pathogenicity of Lp(a). This pathogenicity may be attenuated by measures directed at preventing the activation of those vascular cells that secrete enzymes with a proteolytic potential for Lp(a)/apo(a), namely, leukocytes, macrophages, and T cells.
Scanu
A M
AM
Department of Medicine, The University of Chicago, Illinois 60637, USA.
D000818:Animals; D001158:Arteries / Q000378:metabolism; D001161:Arteriosclerosis / Q000097:blood / Q000209:etiology* / Q000235:genetics; D004730:Endothelium, Vascular / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism; D006801:Humans; D017270:Lipoprotein(a) / Q000235:genetics / Q000378:metabolism*; D009154:Mutation; D011110:Polymorphism, Genetic / Q000235:genetics; D014176:Protein Biosynthesis; D012307:Risk Factors; D013927:Thrombosis / Q000097:blood / Q000209:etiology* / Q000235:genetics
D017270:Lipoprotein(a)