D. Recalde et al., Enhanced fractional catabolic rate of apo A-I and apo A-II in heterozygoussubjects for apo A-I-Zaragoza (L144R), ATHEROSCLER, 154(3), 2001, pp. 613-623
Citations number
70
Categorie Soggetti
Cardiovascular & Respiratory Systems","Cardiovascular & Hematology Research
We have recently reported a new apolipoprotein (apo) A-I variant (apo A-I-Z
aragoza L144R) in a Spanish family with HDL-C levels below the 5th percenti
le for age and sex and low apo A-I concentrations. All the apo A-I-Zaragoza
subjects were heterozygous and none of them showed evidence of coronary ar
tery disease (CAD). Mean plasma HDL-C, apo A-I, and apo A-II levels were lo
wer in apo A-I-Zaragoza carriers as compared to control subjects (40, 60. a
nd 50%, respectively). Lipid composition analysis revealed that apo A-I-Zar
agoza carriers had HDL particles with a higher percentage of HDL triglyceri
de and a lower percentage of HDL esterified cholesterol as compared to thos
e of control subjects. Lecithin:cholesterol acyltransferase (LCAT) activity
and cholesterol esterification rate of apo A-I-Zaragoza carriers were norm
al. Apo A-I and apo A-II metabolic studies were performed on two heterozygo
us apo A-I-Zaragoza carriers and on six control subjects. We used a primed
constant infusion of [5,5,5-H-2(3)]leucine and HDL apo A-I and apo A-II tra
cer/tracee ratios were determined by gas chromatography mass spectrometry a
nd fitted to a monoexponential equation using SAAM II software. Both subjec
ts carrying apo A-I-Zaragoza variant showed mean apo A-I fractional catabol
ic rate (FCR) values more than two-fold higher than mean FCR values of thei
r controls (0.470+/-0.0792 vs. 0.207+/-0.0635 day(-1), respectively). Apo A
-I secretion rate (SR) of apo A-I-Zaragoza subjects was slightly increased
compared with controls (17.32+/-0.226 vs. 12.76+/-3.918 mg kg(-1) day(-1),
respectively). Apo A-II FCR was also markedly elevated in both subjects wit
h apo A-I-Zaragoza when compared with controls (0.366 +/- 0.1450 vs. 0.171/-0.0333 day(-1), respectively) and apo A-II SR was normal (2.31+/-0.517 vs
. 2.1+/-0.684 mg kg(-l) day(-1), respectively). Our results show that the a
po A-I-Zaragoza variant results in heterozygosis in abnormal HDL particle c
omposition and in enhanced catabolism of apo A-I and apo A-II without affec
ting significantly the secretion rates of these apolipoproteins and the LCA
T activation. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.