Journal
CARDIOVASCULAR RESEARCH
Volume 89, Issue 1, Pages 234-243Publisher
OXFORD UNIV PRESS
DOI: 10.1093/cvr/cvq262
Keywords
E prostanoid receptor 4; EP4 receptor; Inflammation; Atherosclerosis; Atherogenesis
Categories
Funding
- National Heart, Lung, and Blood Institute [HL-34636, HL-67429]
- Croucher Foundation
- NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [R03HL067429, R37HL034636, R01HL034636] Funding Source: NIH RePORTER
Ask authors/readers for more resources
Aim Prostaglandin E-2, by ligation of its receptor EP4, suppresses the production of inflammatory cytokines and chemokines in macrophages in vitro. Thus, activation of EP4 may constitute an endogenous anti-inflammatory pathway. This study investigated the role of EP4 in atherosclerosis in vivo, and particularly its impact on inflammation. Methods and results Ldlr(-/-) mice transplanted with EP4(+/+) or EP4(-/-) bone marrow consumed a high-fat diet for 5 or 10 weeks. Allogenic bone marrow transplantation promoted exacerbation of atherosclerosis irrespective of EP4 genotype, compatible with prior observations of exacerbated atherogenesis by allogenicity. EP4 deficiency had little effect on plaque size or morphology in early atherosclerosis, but at the later time point, mice deficient in EP4 displayed enhanced inflammation in their atherosclerotic plaques. Expression of monocyte chemoattractant protein-1 and interferon-gamma inducible protein 10 increased, and there was a corresponding increase in macrophage and T-cell infiltration. These plaques also contained fewer smooth muscle cells. Despite these changes, mice deficient in EP4 in bone marrow-derived cells at an advanced stage had similar lesion size (in both aorta and aortic root) as mice with EP4. Conclusion This study shows that in advanced atherosclerosis, EP4 deficiency did not alter atherosclerotic lesion size, but yielded plaques with exacerbated inflammation and altered lesion composition.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available