Requirement of JNK2 for Scavenger Receptor A-Mediated Foam Cell Formation in Atherogenesis

• DOI: 10.1126/science.1101909
• Publication Date: 2004-11-26T14:42:48Z
• Authors: 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; Thomas F. Lüscher
• Keywords: Foam cell; Scavenger Receptor; Scavenger; Apolipoprotein E

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 ( mice), but not JNK1 mice, developed less atherosclerosis than do mice. Pharmacological inhibition of JNK activity efficiently reduced plaque formation. Macrophages displayed suppressed foam cell formation caused by defective uptake and degradation modified lipoproteins showed increased amounts the lipoprotein-binding -internalizing scavenger receptor A (SR-A), whose phosphorylation was markedly decreased. Macrophage-restricted deletion sufficient to decrease atherogenesis. Thus, JNK2-dependent SR-A promotes lipids macrophages, thereby regulating formation, critical step