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246 recombinant apolipoprotein ai milano

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246 recombinant apolipoprotein ai milano

  1. 1. Editorial Slide - VP Watch, June 27, 2001, Volume 1, Issue 15
  2. 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. 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. 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. 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. 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.

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