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- W2040982433 abstract "Statins, through HMGCoA reductase inhibition, are potent inhibitors of cholesterol synthesis and are widely used in cardiovascular disease. Recent evidence suggests that the beneficial effects of statins extend beyond their action on serum cholesterol levels. The so called pleiotropic effects can be attributed to reduced production of isoprenoid intermediates such as farnesylpyrophosphate (FPP) and geranylgeranylpyrophosphate (GGPP). We investigated the effects of statins on macrophage activation after platelet phagocytosis. Platelet phagocytosis is known as an alternative mechanism for foam cell formation and macrophage activation in human atherosclerotic plaques. Processing of amyloid precursor protein (APP), present in platelets, to amyloid‐β (Aβ) might be responsible for induction of the inducible nitric oxide synthase (iNOS) in macrophages. It has been reported that statins can affect APP processing not only through reduction of cholesterol levels, but also via other mechanisms such as reduced isoprenylation of small GTP binding proteins. Interferon‐γ primed murine J774 macrophages were incubated with washed human blood platelets for 18 h with or without different statins. Nitrite was quantified in the supernatant as a measure for iNOS activity. Macrophage activation following platelet phagocytosis was reduced in the presence of fluvastatin and atorvastatin, but not with simvastatin and rosuvastatin. Besides 30 μM of simvastatin, there was no effect of statins on LPS‐stimulated macrophages, indicating that LPS activates macrophages via a different pathway than platelets. The effect of fluvastatin could be reversed by mevalonic acid, FPP and GGPP. Our results show that some statins decrease macrophage activation after platelet phagocytosis. This effect may be explained by interference with cholesterol synthesis or through reduced isoprenylation of small GTP binding proteins. Diminished macrophage activation in an atherosclerotic plaque can contribute to plaque stabilisation." @default.
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- W2040982433 date "2005-05-17" @default.
- W2040982433 modified "2023-10-16" @default.
- W2040982433 title "Abstract no.: 4 Effect of statins on macrophage activation after platelet phagocytosis" @default.
- W2040982433 doi "https://doi.org/10.1111/j.1472-8206.2004.00286_4.x" @default.
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