2. High-Dose Recombinant Apolipoprotein A-I Milano
Reduces Macrophage and Lipid Content of Plaques
in Apo E Deficient Mice
0
2
4
6
8
10
12
14
16
18
20
%Plaquearea
apoA-I(m) Saline DPPC
Lipid content
Macrophage
conetnt
PK Shah et al. Circulation 2001 Jun 26;103(25):3047-50
3. Carotid Intima-Media Thickness (IMT) in Carriers of the
Apolipoprotein A-I Milano Mutant, Controls and Persons
With Hypoalphalipoproteinemia
0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
Low-HDL Low-HDL
with Apo A-I
Milano
Mutant
Controls
Mean Carotid
Intimal-Medical
Thickness
Sirtori CR, et al. Circulation 2001 Apr 17;103(15):1949-54
4. Among patients with sever low HDL syndrome, those with the mutant
from of Apo A-I Milano do not experience premature CHD. Sirtori and
colleagues from the Limone sul Garda study found that in patients with
comparing to the wild-type group low-HDL subjects show significant
thickening of the carotids compared with control subjects; the apoA-I(M)
carriers instead show normal arterial thickness. These findings suggest that
carriers of apoA-I(M) mutant may be protected against atherosclerosis
despite low-HDL. (Circulation 2001 Apr 17;103(15):1949-54)
PK Shah and colleagues sought whether a single high dose of
recombinantapoA-I (Milano phenotype) could rapidly reduce plaque lipid
and macrophage content in apoE-deficient mice. They injected high
cholesterol–fed apoE-deficient mice with a single IV injection of saline, a
neutral career, or recombinant apoA-I (M) complexed with the career. After
48 hr Mice receiving recombinant apoA-I(M) had 40% to 50% lower lipid
content and 29% to 36% lower macrophage content in their plaques
compared with the saline and the career -treated mice, respectively. They
suggestedthat this strategy could rapidly change plaque composition toward
a more stable phenotype. (Circulation 2001 Apr 17;103(15):1949-54)
5. Conclusion:
• Apo A-I Milano can slow or regress
atherosclerosis. In mice, the regression can
occur in 48hr after a high dose injection.
• Further studies to clarify the mechanism,
specificity, temporal extent of the effect,
and its potential implication in human
plaque stabilization are warranted.
6. Conclusion:
• Apo A-I Milano can slow or regress
atherosclerosis. In mice, the regression can
occur in 48hr after a high dose injection.
• Further studies to clarify the mechanism,
specificity, temporal extent of the effect,
and its potential implication in human
plaque stabilization are warranted.
