References
Query Results -- Details
MGI Accession ID: MGI:3830800
J Number: J:144376
Other Accession IDs:
Title: Macrophage EP4 deficiency increases apoptosis and suppresses early atherosclerosis.
Authors: Babaev VR; Chew JD; Ding L; Davis S; Breyer MD; Breyer RM; Oates JA; Fazio S; Linton MF
Journal: Cell Metab
Volume: 8
Issue: 6
Date: 2008 Dec
Year: 2008
Pages: 492-501
Review Status: Peer Reviewed
Abstract:
Prostaglandin (PG) E(2), a major product of activated macrophages, has been implicated in atherosclerosis and plaque rupture. The PGE(2) receptors, EP2 and EP4, are expressed in atherosclerotic lesions and are known to inhibit apoptosis in cancer cells. To examine the roles of macrophage EP4 and EP2 in apoptosis and early atherosclerosis, fetal liver cell transplantation was used to generate LDLR(-/-) mice chimeric for EP2(-/-) or EP4(-/-) hematopoietic cells. After 8 weeks on a Western diet, EP4(-/-) --> LDLR(-/-) mice, but not EP2(-/-) --> LDLR(-/-) mice, had significantly reduced aortic atherosclerosis with increased apoptotic cells in the lesions. EP4(-/-) peritoneal macrophages had increased sensitivity to proapoptotic stimuli, including palmitic acid and free cholesterol loading, which was accompanied by suppression of activity of p-Akt, p-Bad, and NF-kappaB-regulated genes. Thus, EP4 deficiency inhibits the PI3K/Akt and NF-kappaB pathways compromising macrophage survival and suppressing early atherosclerosis, identifying macrophage EP4-signaling pathways as molecular targets for modulating the development of atherosclerosis.
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