title: Pathophysiological implication of the structural domains of lipoprotein(a).
abstract: Numerous epidemiological studies have shown that lipoprotein(a) (Lp(a)) is an independent risk factor for the premature development of cardiovascular disease. In spite of such evidence, the structural and functional features of this atherogenic, cholesterol-rich particle are not clearly understood. We have demonstrated the presence of two distinct structural domains in apolipoprotein(a) (apo(a)), which are linked by a flexible and accessible region located between kringles 4-4 and 4-5. We have isolated the Lp(a) particle following removal of the N-terminal domain by proteolytic cleavage; the residual particle, containing the C-terminal domain (comprising the region from Kr 4-5 to the protease domain), is linked to apo B-100 by disulphide linkage, and is termed 'mini-Lp(a)'. Mini-Lp(a) exhibited the same binding affinity to fibrin as the corresponding Lp(a). This finding indicated that the kringles responsible for fibrin binding are restricted to Kr 4-5 to Kr 4-10, an observation consistent with the failure of the N-terminal domain to bind to fibrin. N-terminal fragments of apo(a) have been detected in the urine of normal subjects, thereby indicating that part of the catabolism of Lp(a), which is largely indeterminate, could occur via the renal route.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, Unité U321, Lipoprotéines et Athérogénèse, Hôpital de la Pitié, Paris, France.
authors.forename: T
authors.initials: T
authors.lastname: Huby
authors.forename: J
authors.initials: J
authors.lastname: Chapman
authors.forename: J
authors.initials: J
authors.lastname: Thillet
mesh_terms: D000818:Animals; D001053:Apolipoproteins / Q000737:chemistry; D053241:Apoprotein(a); D001665:Binding Sites; D006801:Humans; D018082:Kringles; D017270:Lipoprotein(a) / Q000737:chemistry* / Q000235:genetics; D008958:Models, Molecular; D011110:Polymorphism, Genetic; D011487:Protein Conformation
chemical_list: D001053:Apolipoproteins; D017270:Lipoprotein(a); D053241:Apoprotein(a)