Age- and Sex-related Differences in Lipoproteins
Containing Apoprotein A-I
Takao Ohta, Shinzabro Hattori, Masaji Murakami,
Soroku Nishiyama, and Ichiro Matsuda
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We Investigated age- and sex-related differences In the structure and composition
of two species of lipoproteins that contain apoprotein (apo) A-I (A-I Lp): lipoproteins
containing apo A-I and apo A-II (Lp A-l/A-ll), and Iipoprotein containing apo A-I but no
apo A-II (Lp A-I), which were isolated by immunoaffinlty chromatography. Sixty
normollpidemlc volunteers were assigned to one of three groups based on their ages
and sexual maturation (Group A, prepubertal; Group B, puberty; and Group C,
postpuberty). In A-I Lp, the levels of total cholesterol, choiesteryi ester, phosphoiipid,
and apo A-I were lower In males during puberty and then remained stable. In Lp A-I/
A-II, there were no age- or sex-related changes In llpids or In apo A-II. Levels of
apo A-I in the females were lower with advance in age, although significant differences were observed only between pre- and postpubertal subjects. In Lp A-I, the
levels of total cholesterol, choiesteryi ester, phosphoiipid, and apo A-I were lower In
males during puberty and remained stable thereafter, as in the case of A-I Lp.
Therefore, the age- and sex-related differences observed in A-I Lp appear to be
primarily due to the differences In Lp A-I. When we take Into account the constancy
of Lp A-l/A-ll levels In all groups, the physiological function of A-I Lp (high density
Iipoprotein) In each Individual may be limited by the Lp A-I levels.
(Arteriosclerosis 9:90-95, January/February 1989)
A
polipoprotein (apo) A-I and apo A-II are major apolipoprotein components of high density lipoproteins
(HDL). The majority of these apolipoproteins in normolipidemic fasting plasma are present in the HDL fraction
(density range 1.063 to 1.21 g/ml), although a minor
portion is associated with apo B-containing Iipoprotein
and is present in the less dense fractions.1 Recent studies
concerning HDL metabolism have shown the importance
of apo A-I and apo A-II of HDL particles in determining
physiological role and metabolic fate.2-5 Therefore, it
seems that lipoproteins should be isolated by apolipoprotein composition and not by density.
In recent years, McVicar et al.6 and Cheung and
Albers1 independently isolated apo A-I containing lipoproteins (A-I Lp) by immunoaffinity chromatography and
found that A-I Lp had a chemical nature similar to that of
HDL. Furthermore, Cheung and Albers divided A-I Lp into
two subspecies using anti-apo A-I and anti-apo A-II
immunosorbent columns: lipoproteins containing apo A-I
and apo A-II (Lp A-l/A-ll), and lipoproteins containing apo
A-I but no apo A-II (Lp A-I). These lipoproteins also
showed HDL-like characteristics in terms of particle size,
electrophoretic mobility, and lipid and apolipoprotein com-
positions, and they appeared to be more native than HDL
because uttracentrifugation was not involved in the isolation. Thus, characterization of A-I Lp, Lp A-l/A-ll, and
Lp A-I should aid in elucidating the pathophysiological role
of native HDL in atherosclerosis.
In a previous report,7 we described sex differences of
lipid and apolipoprotein compositions of A-I Lp, Lp A-l/A-ll,
and Lp A-I in normolipidemic adults; lipid levels of A-I Lp
and lipid and apo A-I levels of Lp A-I were higher in
women than in men. This difference may be associated
with the sex difference in the incidence of coronary artery
disease, which is higher in men than in women before
menopause. Therefore, the present study was designed
to gain further insight into sex differences by studying
prepubertal and pubertal children as well as mature
adults. We found that while decreases in plasma A-I Lp
and Lp A-I do occur at puberty in boys, no sex- or
age-related differences occur in the case of Lp A-l/A-ll.
Methods
Subjects
The 60 normolipidemic subjects studied were volunteers from the staff at Kumamoto University or their
children. All were from different nonrelated families (nonconsanguinous). These subjects were divided into three
groups based on age and degree of sexual maturation.
Sexual maturation was determined by visual assessment
of secondary sex characteristics, according to the method
of Tanner.8 The rating for sexual maturation ranged from
I to V (complete development) according to the stages of
female breast or male genitalia development. Each
group included ten males and ten females: Group A,
From the Departments of Pediatrics and Neurosurgery, Kumamoto University Medical School, Kumamoto, Japan.
This work was supported in part by Qrant-in-aid No. 74662770672 for Scientific Research from the Ministry of Education,
Science, and Culture of Japan and by the Uehara Memorial
Foundation.
Address for reprints: Dr. Takao Ohta, Department of Pediatrics,
Kumamoto University Medical School, Honjo 1-1-1, Kumamoto
City, Kumamoto 860, Japan.
Received March 29,1988; revision accepted August 10,1988.
90
LIPOPROTEINS CONTAINING APO A-l
Tanner I and II, ages 6 to 10 years old; Group B, Tanner
III and IV, ages 11 to 15 years old; Group C, Tanner V,
ages 17 to 35 years old.
Diabetes mellitus, liver, and thyroid dysfunctions were
absent in all subjects. There was no obesity (more than
20% of desirable weight). No subject was taking any drug
known to influence lipoprotein metabolism, and there
were no dietary restrictions. Informed consent was obtained
from all subjects and both parents.
Venous blood was drawn into Vacutainer tubes containing disodium EDTA (1.5 mg/ml) after an overnight fast,
and the plasma was promptly separated by low-speed
centrifugation at 4°C.
Ohta et al.
91
performed according to the method of Weber and Osbom.17
The Stokes diameters of the isolated particles were estimated by gradient polyacrylamide gel electrophoresis on
Pharmacia precast PAA 4/30 gels according to the procedure of the manufacturer (Pharmacia, Uppsala, Sweden).
Thyroglobulin, apoferritin, catalase, lactate dehydrogenase, and bovine albumin (Pharmacia) were used as the
calibrating proteins. The Stokes diameters of these calibrating proteins are: thyroglobulin, 17.0 nm; apofenitin,
12.2 nm; catalase, 10.4 nm; lactate dehydrogenase, 8.2
nm; and bovine albumin, 7.5 nm.
Statistical Evaluation
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Procedures
The Wilcoxon signed rank test was used to evaluate the
data.
Isolation of Two Species of Apo A-l Containing
Lipoprotein by Immunosorbent Column
Results
Plasma LlpId and Apollpoproteln Levels
The two species of apo A-l containing lipoproteins were
isolated from plasma by combination of anti-apo A-l and
anti-apo A-ll immunosorbent columns described in detail
previously. 7910 Briefly, flesh plasma (3 ml) was applied on
an anti-apo A-l immunosorbent column (1.5x10 cm).
After washing extensively with 0.01 M Tris, 0.5 M NaCI,
1 mM EDTA, pH 7.5 (buffer A), the column was eluted
with 15 ml of 0.1 M acetic acid, 1 mM EDTA (pH 3.0) at a
flow rate of 20 ml/h. Each effluent was immediately
adjusted to pH 7.4 with 1.0 M Tris solution and dialyzed
against 0.15 M NaCI and 1 mM EDTA, pH 7.4 (buffer B).
Finally, the sample was concentrated to 9 ml in an Amicon
ultrafiltration cell equipped with a PM-10 membrane. A
portion (3 ml) of this sample was used for analysis of
apolipoproteins and lipids. The remaining portion (6 ml)
was used to separate the A-l Lp into Lp A-l/A-ll and Lp A-l.
The sample was applied on an anti-apo A-ll immunosorbent column. The column was washed with buffer A to
obtain the unbound fraction (Lp A-l). The bound fraction
(Lp A-l/A-ll) was eluted with 0.1 M acetic acid, 1 mM
EDTA (pH 3.0). Both the unbound and bound fractions
were dialyzed and then concentrated with an ultrafittration
apparatus (Amicon) to 6 ml in buffer B.
The plasma lipid and apolipoprotein levels in the subjects are summarized in Table 1. In Group B, the levels of
total cholesterol and phospholipid in males were significantly lower than those in females (p<0.01 or 0.005). In
Group C, triglyceride levels in males were significantly
higher than those in females (p<0.05).
Concerning the relationship among the three groups,
the levels of total cholesterol in Group C males were
significantly higher than those in Groups A and B males
(p<0.025 or 0.005). Phospholipid levels in Group B males
were significantly lower than those in Groups A and C
males, and those in Group A females were significantly
lower than those in Groups B and C females (p<0.05).
Apo A-l levels in Group A males were significantly higher
than those in Groups B and C males (p<0.05 or 0.025).
The groups did not differ significantly in plasma levels of
apo C-ll, apo C-lll, or apo E.
All of the plasma lipid and apolipoprotein levels in the
subjects were within normal range for Japanese.11
Protein and Lipid Analysis
The apo A-l, apo A-ll, apo C-ll, apo C-lll, and apo E
concentrations of plasma, A-l Lp, Lp A-l/A-ll, and Lp A-l
were measured by radial immunodiffusion assay as
described previously.7911 Cholesterol and triglyceride concentrations of plasma, A-l Lp, Lp A-l/A-ll, and Lp A-l were
analyzed on an ABA 100 Autoanalyzer (Abbott Laboratories) by enzymatic methods.1213 Cholesteryl ester was
measured by the enzymatic method and fluorometry.14
Phospholipid was analyzed by the method of BartJett.15 The
protein content of each fraction from the immunosorbent
columns was determined by the method of Lowry et al. 18
Electrophoretic Analysis
Agarose gel electrophoresis was performed using a
Pol-E Film system for lipoprotein electrophoresis (Coming)
at pH 8.6, followed by staining with fat red 7B. Slab gel
electrophoresis of lipoproteins isolated in 15% polyacrylamide gels containing 0.1% sodium dodecyl sulfate was
LlpId and Apollpoproteln Compositions of
Lipoproteins Containing Apo A-l
The lipid and apolipoprotein compositions of A-l Lp are
shown in Table 2. In Groups B and C, the levels of total
cholesterol, cholesteryl ester, and phospholipid were significantly lower in males than in females (p<0.01 or
0.005). The levels of total cholesterol, cholesteryl ester,
and phospholipid in Group A males were significantly
higher than those in Groups B and C males (p<0.05 or
0.01). In Group C, apo E levels were lower in males than
in females (mean±SEM: males, 1.15±0.13; females,
1.83±0.24 mg/dl; p<0.05). The levels of other apolipoproteins were similar in males and females in all groups,
and there were no differences among groups. The molar
ratio of apo A-l to apo A-ll was slightly higher in females in
both Groups B and C, but the differences were only
significant in Group B (mean±SEM: males, 2.5±0.08;
females, 2.78±0.08; p<0.01).
LlpId and Apollpoproteln Compositions of
Lipoproteins Containing Apo A-l and Apo A-ll
The lipid and apolipoprotein compositions of Lp A-l/A-ll
are shown in Table 3. The levels of all lipids were similar
92
ARTERIOSCLEROSIS
VOL 9, No 1, JANUARY/FEBRUARY 1989
Table 1. Plasma Llplds and Apollpoprotein Concentrations
Group
Mean age*
(yrs)
Total cholesterol
Trig lyce ride
Phospholipid
8.4
(6 to 10)
8.2
(6 to 10)
159.3±5.0
82.5±12.5
190.7±5.4
148.9±4.6-, -
34.3±1.6
160.3±5.8
74.9+9.5
184.1 ±3.8
141.1 ±6.4 a
34.0+1.0
13.0
(11 to 15)
12.7
(11 to 15)
150.4±5.
73.5±6.0
170.1 ±5.6-i
132.6±4.6-' b
32.8±1.5
174.8±3.5-
80.8±13.0
196.3±4.0-J
139.7±4.2
31.2±1.3
M
24.4
(17 to 35)
185.0±8.2
83.5+11.0-,
189.9±7.1
136.6±3.6 "
33.3±1.2
F
23.8
(17 to 33)
178.1 ±9.3
54.3±5.0 J
198.4±7.5
134.6±4.5
30.0±1.8
Sex
M
F
M
F
Apo A-ll
Apo A-l
Values are mg/dl (mean±SEM).
There were 10 males and 10 females In each group.
The age range is in parentheses, a, p<0.05; b, p<0.025; c, p<0.01; d, p<0.005.
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Table 2. LIpId and Apollpoprotein Concentrations of Lipoproteins Containing Apoprotein A-l
Group
Sex
M
A
F
M
B
F
M
C
F
Total cholesterol
71.9+2.3-, -,
68.1 ±4.8 b
Cholesteryl ester
52.5±1.5n -|
49.4±3.7 b
Triglyceride
19.5±2.5
18.4±2.1
62.9±1.6^ b
74.8±2.9JC
46.4±1.1^ a
55.7±1.9JC
16.1 ±1.7
18.1 ±2.3
62.7±3.0-, 76.3±1.3-l b
46.6±2.0^55.9±0.9-r
18.0±3.4
14.8±1.3
Phospholipid
120.9±4.6-| -,
109.1 ±6.0 b
Apo A-l
Apo A-ll
147.3±4.6-i -|
142.2±6.4 b
33.6±1.6
33.2±1.0
100.2±3.5: a
121.5±3.6JC
131.7±4.6"'
138.5±4.2
31.8+1.5
30.7±1.3
97.1 ± 4 . 8 ^ 122.2±3.5-IC
135.1 ±3.0
133.5±4.1
a
-
33.1 ±1.1
29.6±1.9
Values are mg/dl (mean±SEM).
Each group comprised 10 female and 10 male subjects.
a, p<0.05; b, p<0.01; c, p<0.005.
Table 3. LIpId and Apollpoprotein Concentrations of Lipoproteins Containing Both Apoprotein A-l and Apoprotein A-ll
Group
A
Sex
M
F
B
M
F
C
M
F
Total cholesterol
40.4±1.1
38.8±1.7
Cholesteryl ester
Triglyceride
30.6±0.9
29.9±1.9
39.2±1.3
39.8±0.9
38.7±1.2
40.4±1.3
9.4+1.1
9.8±1.2
Phospholipid
69.6+1.6
66.0±2.7
Apo A-l
88.5±2.5
85.8±3.3
Apo A-ll
29.8±0.9
30.8±0.8
8.9±0.9
9.2±1.5
65.8±2.8
67.8±1.4
84.8±3.0
80.4±3.2
29.4±0.9
30.5±1.0
9.3±1.7
7.5±0.8
63.0±1.9
68.9±3.7
84.2±3.0 n
a
75.0±2.9-l -I
-
34.0+1.6
33.5±1.0
31.7±1.5
b 30.9±1.3
32.5±1.1
29.8±1.2
Values are mg/dl (mean±SEM).
Each group comprised 10 female and 10 male subjects.
a, p<0.05; b, p<0.01.
in both sexes in all groups, and differences among the
groups were nil. In Group C, the levels of apo A-l were
higher in males than in females, but apo E levels were
lower in males than in females (apo E mean±SEM:
males, 0.76+0.06; females, 1.37±0.21 mg/dl; p<0.05).
Apo A-l levels in Group C females were significantly lower
than those in Group A females (p<0.01). Apo C-lll levels
in Group B females were significantly higher than those in
Groups A and C (mean±SEM: Group B, 2.82±0.14;
Group A, 2.33±0.17; Group C, 2.22±0.20 mg/dl; p<0.05).
The levels of apo A-ll and apo C-ll were similar in both
sexes, in all groups, and among groups. The molar ratio of
apo A-l to apo A-ll was fairly constant in all groups.
LIpId and Apollpoprotein Compositions of
Lipoproteins Containing Apo A-l Only
The lipid and apolipoprotein compositions of Lp A-l are
shown in Table 4. In Groups B and C, the levels of total
cholesterol, cholesteryl ester, and phospholipid were significantly lower in males than in females (p<0.05 or p<0.005).
The triglyceride levels were similar in males and females in
all groups, and there was no difference among groups. The
LIPOPROTEINS CONTAINING APO A-l
Table 4.
Group
93
Ohta et al.
Lipid and Apollpoprotein Concentrations of Lipoprotelns Containing Only Apoprotein A-l
Sex
Total cholesterol
M
F
31.4±2.3-,
29.3+3.9
21.9+1.5-1 19.4+2.5 a
M
F
.9±2.3-lC
34.9
16.7±0.9: a
25.0±1.6-lC
M
F
24.0±1.9-,
35.9*1.4-1°
17.2±1.3-, •
25.3+0.9-1°
Cholesteryl ester
Triglyceride
Phospholipid
ApoA-l
ApoA-ll
51.3±3.7-, 44.2±4.9 c
60.4±3.4n 55.2±4.0 c
0±0
0±0
7.2±0.9
9.0±0.8
34.4±2.5i c
53.6±3.4JC
477+2.0: c
59.3+2.3-1°
0±0
8.7±1.8
7.1+0.8
34.1 ±3.4-, 55.9±2.3-l°
50.7±2.1-, 59.6±3.0-l°
0±0
10.2±1.6
8.8±1.0
0±0
0±0
Values are mg/dl (mean±SEM).
Each group comprised 10 female and 10 male subjects.
a, p<0.05; b, p<0.01; c, p<0.005.
Table 5. Lipid Composition of LIpoprotelns Containing Apoprotelns A-l and A-ll and of LIpoprotelns Containing
Apoprotein A-l Only
Group
A
M
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F
B
M
F
C
Lp A-l/A-ll
LpA-l
Lp A-l/A-ll
LpA-l
Total cholesterol
34.8+0.7
35.6+0.8
34.2+0.8
35.3+1.1
Lp A-l/A-ll
LpA-l
Lp A-l/A-ll
LpA-l
Lp A-l/A-ll
LpA-l
Lp A-l/A-ll
LpA-l
Sex
M
F
% of total lipid
Phospholipid
Triglyceride
Upid ratio (%)
Cholesteryl ester/total cholesterol
75.6+0.7-1
70.2±1.2-'C
76.6±2.0-|c
66.4±2.1 J
58.2+0.5-,
c
54.1±0.6J
57.2±0.9"|c
52.8±1.0"'
7.0+0.9-1
a
10.9+1.2J
34.4+0.6-|
37.4+0.9-1
34.2+0.8
35.8+1.0
58.6±0.5"|c
52.9±1.0"'C
58.1±0.4nc
54.7±0.6 J
7.1+0. 6 ] a
9.7+0.9^
7.8+1.2
9.5+1.1
75.8±1.4-jc
70.1 ±0.7 J
77.1 ±0.9 "| c
71.7±1.0"1
34.8+0.51a
36.3+0.9J
34.9+0.6
36.3+0.9
56.9±0.9 -|c
8.3+1.3 -| b
12.6+1.8^
6.4+0.6 b
7.2+0.7 -I
76.1 ±0.6 "I
c
72.1 ±0.9 -i
75.7±0.4
"1
58.7±0.9 c
56.6±1.0 -I
8.6+1.0ja
70.8±0.5 -1°
Values are mg/dl (mean±SEM).
Each group comprised 10 female and 10 male subjects.
a, p<0.05; b, p<0.025; c, p<0.005.
levels of total cholesterol, cholesteryl ester, and phospholipid in Group A males were significantly higher than those in
Groups B and C males (p<0.05 or 0.005).
Apo A-l levels in Groups B and C were significantly
lower in males than in females (p<0.005), and apo A-l
levels in Group A males were significantly higher than
those in Groups B and C males (p<0.005). Apo C-lll
levels in Group B were significantly lower in males than in
females (mean±SEM: males, 1.32±0.07, females
2.12±0.24 mg/dl; p<0.05). Apo C-lll levels in Group A
males were significantly higher and levels in females were
significantly lower than those in Group B counterparts
(mean±SEM: Group A males, 1.60±0.12; females
1.49±0.15; Group B males, 1.32±0.07; females,
2.12±0.24 mg/dl; p<0.05). The levels of apo C-ll and
apo E were similar in each group and among trie groups.
Percent Lipid Compositions of LIpoprotelns
Containing Apoprotelns A-l and A-ll and of
LIpoprotelns Containing Apoprotein A-l Only
As shown in Table 5, the percent of phospholipid was
significantly higher in Lp A-l/A-ll than in Lp A-l except in
the Group C females (p<0.005). In this group, the
percent of phospholipid in Lp A-l was significantly lower
in males than in females (p<0.005). The percent of
triglyceride in all group males and Group A females was
significantly lower in Lp A-l/A-ll than in Lp A-l (p<0.05 or
0.025). In Group C, the percent of triglyceride in Lp A-l
was significantly higher in males than in females
(p<0.05). The percent of total cholesterol in Groups B
and C males was significantly lower in Lp A-l/A-ll than in
Lp A-l (p<0.025). The ratios of cholesteryl ester to total
cholesterol of Lp A-l in the three groups were significantly lower than those in Lp A-l/A-ll (p<0.005) and
there was no difference between sexes.
Apoprotein C-ll/C-lll Ratios In Both Types of
LIpoprotelns
As shown in Table 6, the apo C-ll/apo C-lll ratio in Lp
A-l/A-ll was significantly lower than in the case of Lp A-l
(p<0.005).
Particle Diameter of LIpoprotelns Containing
Apoprotelns A-l and A-ll and of LIpoprotelns
Containing Apoprotein A-l Only
The Lp A-l had two distinct particle sizes: Stokes
diameters of 11.1 ±0.4 nm and 8.8±0.2 nm (mean±SD).
Lp A-l/A-ll exhibited three distinct particle sizes: Stokes
94
ARTERIOSCLEROSIS
VOL 9, No 1, JANUARY/FEBRUARY 1989
Table 6. Apo C-ll/Apo C-lll Ratio in Lipoprotelns Containing Apoprotelns A-l and A-ll and In Lipoproteins
Containing Apoproteln A-l Only
Group A
Males
Lp A-l/A-ll
LpA-l
0.31 ±0.03-,
0.48±0.0 4-l a
Group B
Females
Males
Group C
Females
0.28±0.03-|
0.30±0.02-,
0.48±0.05-l a
0.45±0.03-l a
0.25±0.04-,
0.41±0.04-l a
Males
0.29+O.CKU
a
0.43±0.0f J
Females
0.23±0.02-.
0.45+0.03Ja
Values are mg/dl (mean±SEM).
Each group comprised 10 female and 10 male subjects.
a, p<0.005.
diameters of 10.1 ±0.5 nm, 9.0±0.3 nm, or 8.1 ±0.3 nm
(mean±SD). The Stokes diameters of these particles
were similar in both sexes and in all three groups.
Discussion
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There are other reports on A-l Lp and its subspecies,
which were isolated by immunoaffinity chromatography.16
However, attention was directed to the chemical structures of these lipoproteins. Age- and sex-related differences and physiological functions were not documented.
By contrast, our present study sheds light on these factors
and provides new findings that sex differences of A-l Lp
and Lp A-l were evident during the pubertal stage, as
there was a decline in the major components of these
lipoproteins in the male subjects.
In the literature, age- and sex-related changes were
observed in plasma cholesterol, low density lipoprotein
cholesterol (LDL-C), and HDL cholesterol (HDL-C); there
was a significant decrease in HDL-C in males during
puberty and a later increase in LDL-C. These changes led
to decreased plasma cholesterol levels during puberty
and increased levels after puberty in males. 1821 In consideration of the similarity between HDL and A-l Lp, our
lipid and apolipoprotein data of A-l Lp in males confirmed
these reports and further extended the findings to phosphoiipid, cholesteryl ester, and apo A-l, although the
apo A-l levels remained stable after puberty. In female
subjects, the only age-related changes were in plasma
phosphoiipid levels. This observation and the finding that
phosphoiipid levels in females in A-l Lp were fairly constant suggest that phospholipid-rich LDL particles
increased during and after puberty in females. While the
mechanism for the decrease of A-l Lp in males during
puberty is not well understood, it has been proposed that
plasma testosterone or the interaction of estradiol and
testosterone may be a significant determinant of plasma
HDL-C levels.20 Although we did not do a hormonal
analysis, we did compare our results with hormonal observations on Japanese children.21 Similar to Caucasian
children, plasma testosterone in males and estradiol in
females begin to increase around 11 years of age. Thus,
we speculate that our conclusions may apply to the
components of A-l Lp. It has been reported that administering estrogen to premenopausal women results in a
striking increase in HDL components.22 Our female subjects showed no age-related changes in A-l Lp components, despite possible increases in plasma estradiol
levels. The relationships between sex hormones and A-l
Lp components in females seem to be more complex.
Except for apo A-l, only apo E levels in A-l Lp after puberty
were higher in females. Williams et al. 23 show that phosphoiipid liposomes acquire apo E in plasma and block
cholesterol loading of cultured macrophages. Our results
showing apo E in A-l Lp may be explained by the fact that
phosphoiipid is rich in A-l Lp in females.
HDL2 (1.063<d<1.125), and HDL3 (1.125<d<1.21)
are widely accepted as subspecies of HDL. HDL2 cholesterol is apparently higher in females than in males older
than 20 years of age. 2425 In addition, the levels of HDL2
cholesterol are strongly and inversely correlated with the
incidence of coronary heart disease. 242526 However, even
in these lipoproteins, age- and sex-related changes in
other components such as apolipoproteins, phosphoiipid,
cholesteryl ester, and triglyceride have remained obscure.
Nestruck et al. 27 reported that lipoproteins containing
apo A-l but no apo A-ll (their fractions 1 and 2) were
HDL2-like, and that lipoproteins containing apo A-l and
apo A-ll (their fractions 4 to 6) were HDL3-like, as determined from their hydrated densities.27 Atmeh et al., 28
using immunoprecipitation procedures, found that approximately 70% of the particles in HDL2 contained apo A-l but
no apo A-ll, and that 67% and 33% of these particles were
found in HDL2 and HDL3, respectively. They also found
that HDL3 comprised mainly lipoproteins containing apo
A-l and apo A-ll. Although our Lp A-l and Lp A-l/A-ll were
not similar to their lipoproteins because of different procedures used for isolation, all these data suggest a close
relationship between HDL2 and Lp A-l and between
HDL3 and Lp A-l/A-ll. Thus, the present findings that
major components of Lp A-l were higher in females than
males during and after puberty and that major components of Lp A-l/A-ll (except apo A-l) were fairly constant
indicate that the characteristics of HDL2 and HDL3
reported 242526 may depend mostly on those of Lp A-l
and Lp A-l/A-ll, respectively.
Huff et al.M found that apo C-ll and apo C-lll in HDL
had a similar metabolic pathway, but the apo C in the HDL
subspecies was not reported. Our present study shows
that apo C-ll and apo C-lll were distributed unevenly in
subspecies of A-l Lp, and the apo C-ll/apo C-lll ratio was
higher in Lp A-l than in Lp A-l/A-ll. These results suggest
that, as in the case of whole HDL, apo C-ll and apo C-lll
may have a similar metabolic pathway but (as in the
subspecies) they may have a different pathway.
The particle sizes of our Lp A-l/A-ll and Lp A-l were
consistent with the findings of Cheung and Albers.1 We
found no age- and sex-related differences in the particle
sizes of Lp A-l/A-ll and Lp A-l. Therefore, age- and
LIPOPROTEINS CONTAINING APO A-l
sex-related changes of Lp A-l and Lp A-l/A-ll in normolipidemic subjects do not affect the particle size. Thus, a
decline of Lp A-l levels during the pubertal stage in the
male subjects may be due to the decreased number of Lp
A-l particles.
In conclusion, when we take into account the constancy
of Lp A-l/A-ll levels in all groups and the higher percent of
cholesterol in Lp A-l than in Lp A-l/A-ll in Groups B and C
males, it is likely that differences in physiological function
(ability for reverse cholesterol transport) of A-l Lp (HDL) in
each individual may be limited by the Lp A-l levels.
Furthermore, our studies of patients with chronic renal
failure and of obese subjects (both of whom are at high
risk for coronary heart disease) indicate that Lp A-l was
selectively decreased (Ohta T et al., unpublished observation). This evidence suggests that Lp A-l may be
responsible for the sex difference in the incidence of
coronary heart disease.
12.
13.
14.
15.
16.
17.
18.
19.
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Acknowledgments
We are grateful to Tamami Yuki for excellent technical assistance, Mariko Ohara for comments on the manuscript, and Mieko
Hongo for manuscript typing.
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Age- and sex-related differences in lipoproteins containing apoprotein A-I.
T Ohta, S Hattori, M Murakami, S Nishiyama and I Matsuda
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Arterioscler Thromb Vasc Biol. 1989;9:90-95
doi: 10.1161/01.ATV.9.1.90
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