Requirement of JNK2 for Scavenger Receptor A-Mediated Foam Cell Formation in Atherogenesis
CD36 Antigens
Mice, Knockout
0303 health sciences
Arteriosclerosis
Macrophages
Endothelial Cells
[SDV] Life Sciences [q-bio]
Cholesterol, Dietary
Lipoproteins, LDL
Mice, Inbred C57BL
Mice
03 medical and health sciences
Apolipoproteins E
Cholesterol
Macrophages, Peritoneal
Animals
Diet, Atherogenic
Mitogen-Activated Protein Kinase 9
Mitogen-Activated Protein Kinase 8
Aorta
Cells, Cultured
Bone Marrow Transplantation
Foam Cells
DOI:
10.1126/science.1101909
Publication Date:
2004-11-26T14:42:48Z
AUTHORS (18)
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.
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CITATIONS (234)
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