Sci. Aging Knowl. Environ., 1 December 2004
Requirement of JNK2 for Scavenger Receptor A-Mediated Foam Cell Formation in Atherogenesis
Romeo Ricci, 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, and Thomas F. Lüscherhttp://sageke.sciencemag.org/cgi/content/abstract/2004/48/or21
Abstract: Science 306, 1558-1561 (2004).
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. 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.
Science of Aging Knowledge Environment. ISSN 1539-6150