Reversal of @entity407 with a genetic switch favorably affects the content and inflammatory state of macrophages in XXXX .

@entity407 @entity18901 @entity19 @entity12098 @entity9331 @entity412 @entity731
BACKGROUND: We previously showed that the progression of @entity731 in the Reversa @entity19 (Ldlr(-/- @entity9331 /100Mttpfl/fl) Mx1Cre(+/+)) was arrested when the @entity407 was normalized by inactivating the gene for microsomal @entity412 transfer protein. Here, we tested whether @entity731 would regress if the lipid levels were reduced after advanced plaques formed. METHODS AND RESULTS: Reversa @entity19 were fed an atherogenic diet for 16 weeks. Plasma lipid levels were then reduced. Within 2 weeks, this reduction led to decreased monocyte-derived ( @entity18901 (+)) cells in @entity731 and was associated with emigration of these cells out of plaques. In addition, the fall in lipid levels was accompanied by lower plaque lipid content and by reduced expression in plaque @entity18901 (+) cells of inflammatory genes and higher expression of genes for markers of antiinflammatory M2 macrophages. Plaque composition was affected more than plaque size, with the decreased content of lipid and @entity18901 (+) cells balanced by a higher content of collagen. When the reduced lipid level was combined with the administration of @entity12098 to simulate the clinical aggressive lipid management and proliferator-activated receptor-y agonist treatment, the rate of depletion of plaque @entity18901 (+) cells was unaffected, but there was a further increase in their expression of antiinflammatory macrophage markers. CONCLUSION: The Reversa @entity19 is a new model of @entity731 regression. After lipid lowering, favorable changes in plaque composition were independent of changes in size. In addition, plaque @entity18901 (+) cells became less inflammatory, an effect enhanced by treatment with @entity12098 .
