Heart,
Lung
and Circulation
48th Annual
2000; 9
CYCLODEXTRINS
ACTING
AS SINKS AND SHUTTLES
DIFFERENTIALLY
MOBILISE
FREE AND ESTERIFIED
CHOLESTEROL
FROM HUMAN
FOAM CELLS
S LIU . R.T. Dean2. W. Jessuo2. L. Kritharides’l s3
Clinical Fteseaicii13 and Cell Biology2 Groups The Heart Research Institute,
and Dept. Cardiology Concord Hospita13, Sydney, Australia.
Cholesterol
acceptors
can remove cholesterol
from cells and
retain it (acting as sinks) or can deliver cholesterol
to larger low
efficiency
acceptors
(acting as shuttles).
It is unknown
if these two
processes
are equivalent
for human foam cells. Our aim was to
investigate
whether cyclodextrfns
(CD) with high cholesterol
affinity
acting as sinks, or low cholesterol
affinity and acting as shuttles to
phospholipid
vesicles
(PV), deplete esterified
cholesterol
(EC) and
free cholesterol
(C) from primary
human foam cell macrophages
(HMFC) with equal efficacy.
Primary
human
monocyte-derived
macropha
es
were
incubated with acetylated
low density
lipoprotein
radiola L lled with
3H-C to generate HMFC. HMFC were incubated for up to 24 hrs in
medium containing
PV (200 pg/ml), CD (1.0 m f ml) with diffenng
:.
affinity for C (low affinity hydroxypropyl-CD,
hp- D, or hrgh afflnlty
trimethyl-CD,
tm-CD), and hp-CD or tm-CD with PV. Cells and media
were analysed
for C and EC by HPLC, TLC and radiometric
detection.
Within 2 hrs, tm-CD depleted C to 42.3*10%
of HMFC in
control medium, but did not deplete CE even after 24 hrs (95.0+6.1%
of HMFC control). ho-CD caused minimal C efflux on its own. but with
PV depleted C td 36.7*5.0%
and CE to 35.2*4.9%
of HMFC’control
at
24 hrs. tm-CD
with PV was also ineffective
at depleting
EC
(102.5&.0%
of control cells), thus precluding acceptor saturation
as
the mechanism for poor depletion by tm-CD. Initial cholesterol
efflux at
IO minutes to tm-CD (1.3*0.2%
of total cholesterol),
hp-CD+PLV
(2.2&0.3%)
and tm-CD+PV
(3.&0.5%)
did not correlate
with the
relative efficacy of later CE depletion.
In conclusion,
CE depletion by CDs and PLV does not
necessarily
correlate
with efficiency
of initial cholesterol
efflux.
Dissociated
FC and CE depletion during efflux to tm-CD may indicate
restricted efflux to CDs acting as sinks, and has important implications
for therapeutic cholesterol
removal in vivo.
COMPARISON
OF A MEDITERRANEAN
@led) DIET
TO
LOW FAT (LF) DIET ON LIPIDS
IN PATIENTS
(pts) WITH
CORONARY
HEART
DISEASE
(CHD).
D
et. B Gallag-.
Core
Research Group’, University
of Queensland’,
The Wesley Hospita13,
GriMith University4,
Brisbane, Australia for OLIVE Group
Objective:
To comuare LF to Med diet effects on liuids and maior
lipoproteins
in pts with CHD on statin therapy.
Method: 68 pts with CHD documented by coronary angiography were
randomised to LF (20-25% energy (E) from fat and 8-10% saturated) or
Med (35-40% E from fat and >50% of fat being monounsahuated).
Lipids
were measured prior to lipid lowering drug therapy, at randomisation (x2)
and 3mths (x2).
Results: At randomisation
and 3mths 86%pts LF and 80% pts Med
were on statins. Similarly,
80% LF and 85% Med pts were taking
Pre Statin
CLF & Med)
6.59
2.81
1.18
3.92
LF (n=34)
Med (n=34)
WkO
3 mths
WkO
3 mths
4.48
1.59
4.44
1.63
1.11
2.61
1.17
2.51
4.43
1.48
1.17
2.58
4.34
1.38
1.2
2.46
Conclusion:
A Med diet is as efficacious
for lipid management
as a
LF diet in pts with CHD
on statin therapy.
Current
dietary
recommendations
for CHD could consider a Med diet as a treatment
and preventative
dietary option. This would extend choice for pts
and possibly enhance adherence.
Scientific
Meeting
of CSANZ
A113
DIETARY
MISCONCEPTIONS
AND MISSED
OPPORTUNITIES
TO HELP PATIENTS
LOWER
CORONARY
HEART
DISEASE
(CHD) RISK. D_Colauholm * . A Tonkin.
v.
Core Research’, National Heart Foundation’,
Griffith University3,
Brisbane, Australia
Objective:
To assess community
knowledge
of blood cholesterol,
diet,
adherence to diet advice and to assess extent of screening and diet
advice given by doctors.
Method: Two national telephone surveys were conducted throughout
Australia of 1200 and 725 respondents.
Stratified random sampling
was used. Data were analysed according to gender, age, and
geographical
area. Data was weighted to reflect population density.
Results: There was high awareness of blood cholesterol
as a risk factor
(88.3%). But 45.1% did not know the safe upper limit. 32.4% had
blood cholesterol
measured in last 12 months but 33.5% had never had
it measured by their doctor. Only 29.3% with high cholesterol
were
given diet advice by their doctor. 75.5% believed that diet had major
impact on cholesterol.
74% correctly identified the need to lower
saturated fats, but incorrectly
40% believed they needed to lower
unsaturated fats. 19.7% found diet adherence difficult.
Reasons for
difficulty:
no time (25.1%), need to give up favourite foods (45.7%),
healthy food not readily available (23.2%), interferes with social
activities (26.1%).
Conclusions:
These data suggest high community
awareness of blood
cholesterol but dietary misconceptions
still exist. Screening by doctors
and diet advice remains unacceptably
low. More public and medical
education is required.
A MEDITERRANEAN
DIET (MED) VS A LOW FAT (LF) DIET
IMPROVES
DEPRESSION
INDEPENDENT
OF CHOLESTEROL
IN
CORONARY
HEART
DISEASE PATIENTS(CHD).
,I Weyers*. D
Core Research Group, Wesley
Medical Centre, Brisbane, Australia.
A low saturated fat diet (LF) has failed to improve CHD outcomes in
most randomised
trials. LF may impact mood. Depression
worsens the
prognosis of patients with CHD independent of biological
risk factors.
CHD mortality for depression RR varies 1.94 to 3.5 over two years.
Objective:
To compare the effect of a low fat diet to a Mediterranean
diet on depression and cholesterol
levels in patients with CHD.
Method:
This is a randomised
diet study of patients with CHD
documented
by coronary angiography.
64 patients were randomised
to
either a low fat (NCEP-Step
II) or a high fat Mediterranean
(~35% E,
50% MUFA).
Patients were assessed for depressive
symptoms
at
baseline and at three-month
using the Beck Depression
Inventory
(BDI-II).
Results: Depression
at baseline and 3 months was 33% and 20% (p =
,603) for LF. For MED 32% and 5% (p < .Ol). Mean BDI at baseline
and 3 months was 7.6 and 6.6 for LF (p = ,343) and 7.8 and 4.6 for
MED (p < .02). A 13% and 46% decrease
respectively.
Mean
cholesterol
at baseline for LF and MED are 4.57 mmol/L
and 4.44
mmoVL with no change at 3 months.
Conclusions:
A MED
but not a LF diet improves
depression
independent of cholesterol
levels.