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 tha t 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 possi ble 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 cl eaved at interkringle sites by the action of enzymes of the elastase f amily generating fragments that differ in structural, functional, and metabolic properties. In the case of Lp[a], elastase digestion generat es a miniLp[a] particle, which contains the apo[a] COOH-terminal domai n 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 atheroscl erotic process. Thus, the apo[a] immunoreactive material, which has be en described in the atherosclerotic plaque, may represent miniLp[a] an d/or apo[a] fragments accumulating in the vessel wall as a function of their relative affinity for the components of the extracellular matri x and producing complexes with an atherothrombogenic potential. This p otential may depend on several factors: kringle folding and conformati on, susceptibility of the linkers to proteolytic cleavage, binding spe cificity of given apo[a] fragments to the matrix components of the art erial intima, and the overall inflammatory status of the arterial wall .