sion. Differences were considered significant at P B 0.05 in the bilateral situation.
3. Results
In this study, we evaluated a group of patients with primary hypertriglyceridemia and low HDL-C levels
group 1, n = 12. Results were analyzed in comparison both to a group of subjects who exhibited normal
plasma triglyceride and low HDL-C levels group 2, n = 12 and to normotriglyceridemic subjects with nor-
mal HDL-C levels group 3, controls, n = 12.
All the subjects were of similar age 47 9 11, 40 9 14, 41 9 12 years, mean 9 S.D.; groups 1, 2 and 3, respec-
tively. The body mass index was moderately higher in patients with hypertriglyceridemia and low HDL-C lev-
els group 1 than in controls group 3 28.0 9 3.6, 27.9 9 3.6, 24.9 9 2.6 kgm
2
; groups 1, 2 and 3, respec- tively; P B 0.05, whereas no statistically significant dif-
ferences were
detected in
the waisthip
ratio 0.96 9 0.07, 0.91 9 0.08, 0.92 9 0.09; groups 1, 2 and 3,
respectively. Fasting insulin levels were similar in the three groups
of subjects 15.4 9 6.5, 11.5 9 4.2, 12.0 9 3.7 mIUml; groups 1, 2 and 3, respectively.
The lipid and lipoprotein profiles from the 36 sub- jects are described in Table 1. As expected, differences
in plasma triglycerides and HDL-C levels emerged from the selection criteria and the constitution of each group.
In hypertriglyceridemic patients the elevation of plasma triglyceride levels was only due to an increased VLDL
concentration and not to the presence of chylomicrons. This was evidenced by an increased band in the preb
position VLDL and absence of band in the origin chylomicron of an electrophoretic run in agarose gel
for lipoproteins. Plasma triglyceride levels from nor- motriglyceridemic subjects with low HDL-C levels
group 2 were within the reference values B 200 mg dl, though significantly higher than control subjects.
Of 12 patients from the above mentioned group 2, nine showed plasma triglyceride levels higher than 150 mg
dl. Total and LDL-cholesterol plasma concentrations were not significantly different in the three groups.
HDL-phospholipids and the cholesterol transported in HDL subfractions, HDL
2
and HDL
3
, were significantly reduced in both groups with low HDL-C levels groups
1 and 2. In contrast, in the high triglyceride group group 1, HDL-triglyceride concentration showed an
elevation when compared to controls.
The results from the apo and lipoprotein particle plasma levels are presented in Table 2. HDL major
apolipoproteins, apo A-I and apo A-II, exhibited sig- nificantly lower levels in both hypoalphalipoproteine-
mic groups groups 1 and 2 than in controls. These reductions were due to a selective decrease in LpA-I:A-
II and not in LpA-I particle concentrations. Apo B
100
was not different in the three groups. Total apo C-III was only increased in patients with high triglyceride
levels group 1 in comparison to both normotriglyceri- demic groups. This elevation reflects higher levels of
both fractions, apo C-III Lp non B and LpB:C-III in the hypertriglyceridemic group of patients as compared
to normotriglyceridemic subjects. Concerning apo E- containing lipoproteins, total apo E plasma concentra-
tion was higher in the group with hypertriglyceridemia than in controls, but in this case, the increment was
only attributable to the LpB:E fraction.
We also calculated the molar ratio HDL-Capo A- I + apo A-II, which was defined by Brinton et al. [30] as
Table 1 Lipid and lipoprotein profile of patients and control subjects mgdl; mean 9 S.D
a
High TG, low HDL-C Normal TG, normal HDL-C
Normal TG, low HDL-C group 2, n = 12
group 3, n = 12 group 1, n = 12
341 9 110
b,c
TG 167 9 22
c
102 9 38 227 9 32
TC 224 9 40
227 9 34 66 9 33
b,c
VLDL-C 33 9 7
e
25 9 11 150 9 30
LDL-C 162 9 39
134 9 39 27 9 6
c
HDL-C 29 9 4
c
53 9 8 HDL
2
-C 3 9 2
d
2 9 2
c
9 9 4 24 9 6
c
HDL
3
-C 27 9 4
c
44 9 6 8.8 9 2.2
c
TCHDL-C 7.8 9 1.6
c
4.3 9 0.4 HDL-PL
40 9 22
c
50 9 14
d
75 9 18 17 9 6
e
13 9 3 HDL-TG
12 9 5
a
HDL, high density lipoprotein; LDL, low density lipoprotein; PL, phospholipids; TC, total cholesterol; TG, triglycerides; VLDL, very low density lipoprotein.
b
PB0.001 versus group 2, by Mann–Whitney U-test.
c
PB0.001 versus group 3, by Mann–Whitney U-test.
d
PB0.005 versus group 3, by Mann–Whitney U-test.
e
PB0.05 versus group 3, by Mann–Whitney U-test.
Table 2 Apolipoprotein and lipoprotein particle levels of patients and control subjects mgdl; mean 9 S.D.
a
Normal TG, low HDL-C High TG, low HDL-C
Normal TG, normal HDL-C group 1, n = 12
group 2, n = 12 group 3, n = 12
apo A-I 117 9 17
b
109 9 14
h
141 9 22 19 9 3
c
20 9 4
c
29 9 3 apo A-II
86 9 15 apo B
100
90 9 13 93 9 11
42 9 7 50 9 9
d
47 9 10 Lp A-I
67 9 13
c
Lp A-I:A-II 67 9 10
c
94 9 19 2.2 9 0.3
3.8 9 1.1
c,e
2.2 9 0.5 Total apo C-III
1.5 9 0.3 apo C-III Lp non B
1.6 9 0.4 2.2 9 0.6
b,g
0.7 9 0.2 1.6 9 0.7
c,e
0.6 9 0.2 LpB:C-III
8.0 9 2.0 7.9 9 2.0
Total apo E 10.9 9 4.0
d
4.2 9 1.8 4.7 9 2.0
4.9 9 1.5 apo E Lp non B
4.0 9 2.7 3.2 9 2.0
LpB:E 6.6 9 4.0
f a
apo, apolipoprotein; HDL-C, high density lipoprotein cholesterol; Lp, lipoprotein particle; TG, triglycerides.
b
PB0.01 versus group 3, by Mann–Whitney U-test.
c
PB0.001 versus group 3, by Mann–Whitney U-test.
d
PB0.05 versus group 2, by Mann–Whitney U-test.
e
PB0.001 versus group 2, by Mann–Whitney U-test.
f
PB0.05 versus group 3, by Mann–Whitney U-test.
g
PB0.005 versus group 2, by Mann–Whitney U-test.
h
PB0.005 versus group 3, by Mann–Whitney U-test. Table 3
Percentual lipid composition of HDL isolated by gel filtration chromatography from patients and control subjects mean 9 S.D.
a
Normal TG, low HDL-C High TG, low HDL-C
Normal TG, normal HDL-C group 1, n = 12
group 3, n = 12 group 2, n = 12
2.8 9 1.1
b
FC 3.2 9 1.2
c
4.2 9 0.5 34.6 9 5.7
d,e
CE 40.8 9 4.6
41.2 9 5.0 32.2 9 10.3
37.2 9 15.2 37.0 9 4.6
PL 23.9 9 11.0
17.5 9 6.8 TG
25.4 9 10.4
c a
CE, cholesteryl esters; FC, free cholesterol; HDL-C, high density lipoprotein cholesterol; PL, phospholipids; TG, triglycerides. Results are expressed as percentages of the lipid mass.
b
PB0.001 versus group 3, by Mann–Whitney U-test.
c
PB0.05 versus group 3, by Mann–Whitney U-test.
d
PB0.01 versus group 2, by Mann–Whitney U-test.
e
PB0.01 versus group 3, by Mann–Whitney U-test.
a predictor of apo A-I fractional catabolic rate 13.7 9 2.8, 15.5 9 1.8, 21.0 9 2.8; groups 1, 2 and 3, respec-
tively. This ratio was significantly lower in both groups with hypoalphalipoproteinemia than in control
subjects groups 1 and 2 vs. group 3; P B 0.001, thus suggesting an increased catabolism of apo A-I in pa-
tients from groups 1 and 2. In addition, plasma triglyc- eride levels showed a negative correlation with the ratio
HDL-Capo A-I + apo A-II r = − 0.69, P B 0.001, n = 36.
The alteration spectrum was not only revealed in HDL apolipoproteins and HDL subclasses, but also in
HDL lipid composition Table 3. Free cholesterol and cholesteryl ester percentages were reduced in HDL
particles, whereas the triglyceride content was signifi- cantly increased in the hypertriglyceridemic group
group 1 in comparison to controls. Cholesterol efflux experiments were carried out using
two different cellular models Fu5AH rat hepatoma and J774 macrophage cells and two different kind of
samples whole serum and HDL fractions Fig. 1. As shown in Fig. 1A and B, serum samples from both
hypoalphalipoproteinemic groups groups 1 and 2 were less efficient in promoting cellular cholesterol
efflux than samples from control subjects in both cell types. Results obtained employing these two cellular
systems incubated with whole serum exhibited a strong direct correlation r = 0.54, P B 0.001, n = 36. In order
to get further information about factors influencing the cholesterol efflux process, we analyzed the correlations
of the capacity to induce cholesterol efflux from Fu5AH and J774 cells with different parameters. Re-
sults are shown in Table 4. As exhibited in Fig. 1C, only HDL fraction from hypertriglyceridemic patients
Fig. 1. Cholesterol efflux from monolayer cultured cells Fu5AH rat hepatoma cells or J774 mouse macrophage cells induced by samples whole serum or HDL fractions from hypertriglyceridemic patients in comparison to normotriglyceridemic subjects with or without low HDL-C levels.
HDL-C, high density lipoprotein-cholesterol; TG, triglycerides.
a
P B 0.001,
b
P B 0.05,
c
P B 0.01 versus normal TG, normal HDL-C group.
group 1 induced cholesterol efflux from Fu5AH cells to a lesser extent than HDL fractions from subjects
with normal triglyceride levels. LCAT activity was lower in both groups with hy-
poalphalipoproteinemia groups 1 and 2 than in con- trols, but this difference was only statistically significant
for the group of subjects with normal triglyceride and low HDL-C levels Table 5.
CETP was evaluated by measuring its activity and its mass. As represented in Table 5, CETP activity was
increased in hypertriglyceridemic patients group 1 in comparison to both groups with normal triglyceride
levels, while CETP mass Table 5 did not show any statistical difference between groups.
We also evaluated the correlations between plasma triglyceride levels and HDL lipids, apolipoproteins,
lipoprotein particles, cholesterol efflux promotion, LCAT activity, and CETP mass and activity Table 6.
4. Discussion
Kategori