Editorial Slide - VP Watch, June 27, 2001, Volume 1, Issue 15

High-Dose Recombinant Apolipoprotein A-I Milano Reduces Macrophage and Lipid Content of Plaques in Apo E Deficient Mice

02468

101214161820

% P

laqu

e ar

ea

apoA-I(m) Saline DPPC

Lipid content

Macrophageconetnt

PK Shah et al. Circulation 2001 Jun 26;103(25):3047-50

Carotid Intima-Media Thickness (IMT) in Carriers of the Apolipoprotein A-I Milano Mutant, Controls and Persons

With Hypoalphalipoproteinemia

00.10.20.30.40.50.60.70.80.9

Low-HDL Low-HDLwith Apo A-I

MilanoMutant

Controls

Mean CarotidIntimal-MedicalThickness

Sirtori CR, et al. Circulation 2001 Apr 17;103(15):1949-54

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 recombinant apoA-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 suggested that this strategy could rapidly change plaque composition toward

a more stable phenotype. (Circulation 2001 Apr 17;103(15):1949-54)

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.