Publication Date:
2004-11-30
Description:
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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ricci, Romeo -- Sumara, Grzegorz -- Sumara, Izabela -- Rozenberg, Izabela -- Kurrer, Michael -- Akhmedov, Alexander -- Hersberger, Martin -- Eriksson, Urs -- Eberli, Franz R -- Becher, Burkhard -- Boren, Jan -- Chen, Mian -- Cybulsky, Myron I -- Moore, Kathryn J -- Freeman, Mason W -- Wagner, Erwin F -- Matter, Christian M -- Luscher, Thomas F -- New York, N.Y. -- Science. 2004 Nov 26;306(5701):1558-61.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Cardiovascular Research, Institute of Physiology, and Division of Cardiology, University Hospital Zurich, CH-8057 Zurich, Switzerland. romeo.ricci@cell.biol.ethz.ca〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/15567863" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
Antigens, CD36/metabolism
;
Aorta/chemistry/pathology
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Apolipoproteins E/genetics
;
Arteriosclerosis/*metabolism/pathology
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Bone Marrow Transplantation
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Cells, Cultured
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Cholesterol/metabolism
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Cholesterol, Dietary/administration & dosage
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Diet, Atherogenic
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Endothelial Cells/physiology
;
Foam Cells/*metabolism
;
Lipoproteins, LDL/metabolism
;
Macrophages/*metabolism
;
Macrophages, Peritoneal/physiology
;
Mice
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Mice, Inbred C57BL
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Mice, Knockout
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Mitogen-Activated Protein Kinase 8/metabolism
;
Mitogen-Activated Protein Kinase 9/genetics/*metabolism
;
Muscle, Smooth, Vascular/cytology
;
Myocytes, Smooth Muscle/physiology
;
Phosphorylation
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Receptors, Immunologic/genetics/*metabolism
;
Receptors, Scavenger
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Scavenger Receptors, Class A
;
T-Lymphocytes/immunology
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
