Lipoprotein(a) and apolipoprotein(a) in a New World monkey, the common marmoset (Callithrix jacchus). Association of variable plasma lipoprotein(a) levels with a single apolipoprotein(a) isoform.
In an earlier report (Chapman et al, Biochemistry 1979;18:5096-5108), we suggested that the common marmoset may represent an important model for the study of human plasma lipoprotein metabolism. We now extend the interest of this monkey model to the study of lipoprotein(a) (Lp[a]) and apolipoprotein(a) (apo[a]). Density gradient ultracentrifugal fractionation of marmoset plasma revealed a bimodal distribution of Lp(a), with one peak of concentration occurring in association with very low density lipoproteins (VLDLs) and a second in the density range 1.040-1.080 g/ml. The dense Lp(a) subspecies displayed physicochemical properties (chemical composition, particle size, and electrophoretic mobility) that closely resembled those of its counterpart in humans and baboons but that were distinct from those of low density lipoprotein (LDL). Furthermore, the particle size of marmoset Lp(a) was invariant (31 nm) over the density interval 1.040-1.080 g/ml, whereas that of LDL decreased progressively with an increase in density (approximately 26-25.2 nm). Use of polyclonal and monoclonal antibodies to human apo(a) and of a polyclonal antibody to marmoset Lp(a) allowed immunologic identification of a single apo(a) isoform in the marmoset whose size was similar to that of apo B-100; apo(a) and apo B-100 were associated in Lp(a) particles by a disulfide linkage. The total protein mass of apo-Lp(a) was estimated to be 800,000 or more by electrophoresis in sodium dodecyl sulfate-polyacrylamide-agarose gels. The amino acid compositions of marmoset and human apo(a) resembled each other but were distinct from those of the corresponding forms of apo B-100. Immunologic evidence is provided for a high degree of cross reactivity between apo(a) in marmosets, baboons, and humans, supporting the idea of the existence of a marked degree of structural homology between these proteins. In addition, electroimmunoblotting of marmoset apo(a) and marmoset plasminogen showed that these proteins shared certain epitopes in common, suggesting that marmoset apo(a) may possess kringle-like structural features. Finally, despite possession of a single apo(a) isoform, marmoset Lp(a) levels varied over a 100-fold range (0.5-49 mg/dl plasma). Considered together, our present findings suggest that the common marmoset monkey constitutes a unique model in which to study the regulation of apo(a) gene expression and the posttranslational processing of apo(a), as well as factors that modulate the synthesis, intravascular metabolism, and cellular catabolism of Lp(a).
Guo
H C
HC
INSERM Unité 321, Hôpital de la Pitié, Paris, France.
Michel
J B
JB
Blouquit
Y
Y
Chapman
M J
MJ
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D016632:Apolipoprotein A-I; D001054:Apolipoproteins A / Q000097:blood*; D001055:Apolipoproteins B / Q000097:blood; D001345:Autoradiography; D002143:Callitrichinae; D002499:Centrifugation, Density Gradient; D002784:Cholesterol / Q000097:blood; D002850:Chromatography, Gel; D003429:Cross Reactions / Q000276:immunology; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D006801:Humans; D017270:Lipoprotein(a); D008074:Lipoproteins / Q000097:blood* / Q000276:immunology / Q000302:isolation & purification; D008297:Male; D010215:Papio; D010958:Plasminogen / Q000276:immunology
D000911:Antibodies, Monoclonal; D016632:Apolipoprotein A-I; D001054:Apolipoproteins A; D001055:Apolipoproteins B; D017270:Lipoprotein(a); D008074:Lipoproteins; D010958:Plasminogen; D002784:Cholesterol