Fk. Welty et al., DECREASED PRODUCTION AND INCREASED CATABOLISM OF APOLIPOPROTEIN B-100IN APOLIPOPROTEIN B-67 B-100 HETEROZYGOTES/, Arteriosclerosis, thrombosis, and vascular biology, 17(5), 1997, pp. 881-888
Apolipoprotein (apo) B-67 is a truncated form of apoB-100 due to delet
ion of an adenine at cDNA 9327. Heterozygotes have one allele making a
poB-100; therefore, plasma apoB levels would be predicted to be at lea
st 50% of normal. However, apoB-67 heterozygotes have total plasma apo
B levels that are 24% of normal. To determine the mechanisms responsib
le for the lower-than-expected levels of apoB, in vivo kinetics of apo
B-100 were performed in three apoB-67/apoB-100 heterozygotes and compa
red with those of six control subjects by using a primed-constant infu
sion of [5,5,5-H-2(3)]leucine in the fed state. Kinetic parameters wer
e calculated by multicompartmental modeling of the data. The mean tota
l apoB plasma concentration of the apoB-67 subjects was 21.8+/-6.1 mg/
dL, or 24% of that of control subjects (89.6+/-24.1 mg/dL, P=.002). Ap
oB-67 subjects had lower mean VLDL apoB-100 production rates (3.6+/-1.
2 versus 13.9+/-3.5 mg . kg(-1) . d(-1), P=.002) and lower mean transp
ort rates of apoB-100 into LDL (3.5+/-1.4 versus 12.6+/-4.1 mg . kg(-1
) . d(-1), P=.008) compared with control subjects. The transport rate
into IDL was not significantly different (1.2+/-0.5 versus 6.2+/-4.0 m
g . kg(-1) . d(-1), P=.07). The fractional catabolic rate of VLDL apoB
-100 was significantly higher in apoB-67 subjects than in control subj
ects (18.1+/-8.6 versus 7.6+/-1.6 mg . kg(-1) . d(-1), P=.017). ApoB-1
00 IDL and LDL fractional catabolic rates were not significantly diffe
rent. VLDL apoB-100 pool size in apoB-67 subjects was 11% of that of c
ontrol subjects (15.8+/-7.7 versus 141.6+/-33.7 mg, P=.0004) due to a
74% lower production rate (26% of control values) and a 2.4-fold highe
r fractional catabolic rate. LDL apoB-100 pool size in apoB-67 subject
s was 22% of that of control subjects (665.3+/-192.4 versus 2968.3+/-7
65.2 mg, P=.002) due primarily to a lower production rate (27% of cont
rol values). Thus, both decreased production of VLDL and LDL apoB-100
and increased catabolism of VLDL apoB-100 are responsible for the low
levels of apoB-100 in apoB-67 subjects.