Requirement of JNK2 for Scavenger Receptor A-Mediated Foam Cell Formation in Atherogenesis
- 26 November 2004
- journal article
- other
- Published by American Association for the Advancement of Science (AAAS) in Science
- Vol. 306 (5701) , 1558-1561
- https://doi.org/10.1126/science.1101909
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. 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.Keywords
This publication has 26 references indexed in Scilit:
- Structural basis for the selective inhibition of JNK1 by the scaffolding protein JIP1 and SP600125The EMBO Journal, 2004
- Class A Scavenger Receptor-mediated Adhesion and Internalization Require Distinct Cytoplasmic DomainsPublished by Elsevier ,2003
- Role of JNK, p38, and ERK in Platelet-Derived Growth Factor–Induced Vascular Proliferation, Migration, and Gene ExpressionArteriosclerosis, Thrombosis, and Vascular Biology, 2003
- Inflammation in atherosclerosisNature, 2002
- A central role for JNK in obesity and insulin resistanceNature, 2002
- Class A scavenger receptors mediate cell adhesion via activation of Gi/o and formation of focal adhesion complexesJournal of Lipid Research, 2002
- Joint damage and inflammation in c‐Jun N‐terminal kinase 2 knockout mice with passive murine collagen‐induced arthritisArthritis & Rheumatism, 2002
- JNK is required for effector T-cell function but not for T-cell activationNature, 2000
- PPARγ Promotes Monocyte/Macrophage Differentiation and Uptake of Oxidized LDLCell, 1998
- Severe hypercholesterolemia and atherosclerosis in apolipoprotein E-deficient mice created by homologous recombination in ES cellsPublished by Elsevier ,1992