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. 2004 Nov 26;306(5701):1558-61.
doi: 10.1126/science.1101909.

Requirement of JNK2 for scavenger receptor A-mediated foam cell formation in atherogenesis

Romeo Ricci  1 , Grzegorz Sumara, Izabela Sumara, Izabela Rozenberg, Michael Kurrer, Alexander Akhmedov, Martin Hersberger, Urs Eriksson, Franz R Eberli, Burkhard Becher, Jan Borén, Mian Chen, Myron I Cybulsky, Kathryn J Moore, Mason W Freeman, Erwin F Wagner, Christian M Matter, Thomas F Lüscher
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Requirement of JNK2 for scavenger receptor A-mediated foam cell formation in atherogenesis

Romeo Ricci et al. Science. .

VSports注册入口 - Abstract

In vitro studies suggest a role for c-Jun N-terminal kinases (JNKs) in proatherogenic cellular processes. We show that atherosclerosis-prone ApoE-/- mice simultaneously lacking JNK2 (ApoE-/- JNK2-/- mice), but not ApoE-/- JNK1-/- mice, developed less atherosclerosis than do ApoE-/- mice. Pharmacological inhibition of JNK activity efficiently reduced plaque formation VSports手机版. Macrophages lacking JNK2 displayed suppressed foam cell formation caused by defective uptake and degradation of modified lipoproteins and showed increased amounts of the modified lipoprotein-binding and -internalizing scavenger receptor A (SR-A), whose phosphorylation was markedly decreased. Macrophage-restricted deletion of JNK2 was sufficient to decrease atherogenesis. Thus, JNK2-dependent phosphorylation of SR-A promotes uptake of lipids in macrophages, thereby regulating foam cell formation, a critical step in atherogenesis. .

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