"Jnking" atherosclerosis.
Numerous studies in animal models established a key role of the C-jun N-terminal kinase (JNK) family (JNK1, JNK2 and JNK3) in numerous pathological conditions, including cancer, cardiac hypertrophy and failure, neurodegenerative disorders, diabetes, arthritis and asthma. A possible function of JNK in atherosclerosis remained uncertain since conclusions have mainly been based on in vitro studies investigating endothelial cell activation, T-effector cell differentiation and proliferation of vascular smooth muscle cells, all of which represent crucial cellular processes involved in atherosclerosis. However, recent experiments demonstrated that macrophage-restricted deletion of JNK2 was sufficient to efficiently reduce atherosclerosis in mice. Furthermore, it has been shown that JNK2 specifically promotes scavenger receptor A-mediated foam cell formation, an essential step during early atherogenesis, which occurs when vascular macrophages internalize modified lipoproteins. Thus, specific inhibition of JNK2 activity may emerge as a novel and promising therapeutic approach to attenuate atheroma formation in the future. In this review, we discuss JNK-dependent cellular and molecular mechanisms underlying atherosclerosis.
Sumara
G
G
Institute of Cell Biology, ETH Zürich (Hönggerberg), Schafmattstrasse 18, 8093, Zürich, Switzerland.
Belwal
M
M
Ricci
R
R
D000818:Animals; D050197:Atherosclerosis / Q000201:enzymology* / Q000473:pathology*; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000502:physiology*
D048031:JNK Mitogen-Activated Protein Kinases