Metabolism of Apo(a) and ApoB-100 in Human Lipoprotein(a)

Abstract

Lipoprotein(a) (Lp(a)) is a plasma lipoprotein highly correlated with cardiovascular and cerebrovascular disease. It contains two major proteins: apoB-100 similar to that present in LDL, and apo(a) which exists in different polymorphic forms with apparent molecular weight (Mr) from 418 to 838 kD. The polymorph Mr is inversely correlated with plasma Lp(a) level, suggesting that the rate of apo(a) synthesis is related to the polymorph size. This possibility has been evaluated by using stable isotope methodology to measure the rates of synthesis of apo(a) in Lp(a) and of apoB-100 in Lp(a), LDL, IDL, and VLDL. The level of isotope enrichment in vivo was used to compute fractional synthesis rates (FSR, d-1) using a non-compartmental model. Five normolipidemic subjects each displaying a unique apo(a) polymorph phenotype were studied. Their mean FSR ± SD values were: Apo(a) in Lp(a) = 0.162 ± 0.084; ApoB in Lp(a) = 0.139 ± 0.073; ApoB in LDL = 0.569 ± 0.157. From a reduced compartmental model the FSR for ApoB in Lp(a) = 0.130 ± 0.063; LDL = 0.680 ± 0.204; IDL = 12.11 ± 15.72; VLDL = 9.10 ± 6.58. Although the negative correlation of apo(a) Mr with Lp(a) level was high (r = -0.872), the correlation of apo(a) FSR with apo(a) Mr. was low (r = 0.341). The rate of apo(a) synthesis in Lp(a) was quite similar to that of apoB in Lp(a), but the latter was only -25% of the FSR for apoB in LDL. The FSR for apo(a) was not correlated with plasma cholesterol levels (r = 0.153) but was negatively correlated with plasma triglyceride levels (r = -0.914).