Requirement of JNK2 for scavenger receptor A-mediated foam cell formation in atherogenesis - PubMed (original) (raw)

. 2004 Nov 26;306(5701):1558-61.

doi: 10.1126/science.1101909.

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

Affiliations

• PMID: 15567863
• DOI: 10.1126/science.1101909

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

Romeo Ricci et al. Science. 2004.

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.

PubMed Disclaimer

Publication types

MeSH terms

Substances

LinkOut - more resources

• Full Text Sources

  • Atypon
  • Ovid Technologies, Inc.

• Other Literature Sources

  • The Lens - Patent Citations Database

• Molecular Biology Databases

  • Mouse Genome Informatics (MGI)

• Research Materials

  • NCI CPTC Antibody Characterization Program

• Miscellaneous

  • NCI CPTAC Assay Portal