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Article: Lack of EP4 receptors on bone marrow-derived cells enhances inflammation in atherosclerotic lesions

TitleLack of EP4 receptors on bone marrow-derived cells enhances inflammation in atherosclerotic lesions
Authors
KeywordsAtherogenesis
Atherosclerosis
E prostanoid receptor 4
EP4 receptor
Inflammation
Issue Date2011
PublisherOxford University Press. The Journal's web site is located at http://cardiovascres.oxfordjournals.org
Citation
Cardiovascular Research, 2011, v. 89 n. 1, p. 234-243 How to Cite?
AbstractAim Prostaglandin E2, 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-γ 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. © 2010 The Author.
Persistent Identifierhttp://hdl.handle.net/10722/139594
ISSN
2015 Impact Factor: 5.465
2015 SCImago Journal Rankings: 2.897
PubMed Central ID
ISI Accession Number ID
Funding AgencyGrant Number
National Heart, Lung, and Blood InstituteHL-34636
HL-67429
Croucher Foundation
Funding Information:

This work was supported in part by grants from the National Heart, Lung, and Blood Institute (HL-34636 to P.L.; HL-67429 to G.S.). E.H.C.T. received a fellowship from the Croucher Foundation.

References

 

DC FieldValueLanguage
dc.contributor.authorTang, EHCen_HK
dc.contributor.authorShimizu, Ken_HK
dc.contributor.authorChristen, Ten_HK
dc.contributor.authorRocha, VZen_HK
dc.contributor.authorShvartz, Een_HK
dc.contributor.authorTesmenitsky, Yen_HK
dc.contributor.authorSukhova, Gen_HK
dc.contributor.authorShi, GPen_HK
dc.contributor.authorLibby, Pen_HK
dc.date.accessioned2011-09-23T05:52:21Z-
dc.date.available2011-09-23T05:52:21Z-
dc.date.issued2011en_HK
dc.identifier.citationCardiovascular Research, 2011, v. 89 n. 1, p. 234-243en_HK
dc.identifier.issn0008-6363en_HK
dc.identifier.urihttp://hdl.handle.net/10722/139594-
dc.description.abstractAim Prostaglandin E2, 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-γ 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. © 2010 The Author.en_HK
dc.languageengen_US
dc.publisherOxford University Press. The Journal's web site is located at http://cardiovascres.oxfordjournals.orgen_HK
dc.relation.ispartofCardiovascular Researchen_HK
dc.subjectAtherogenesisen_HK
dc.subjectAtherosclerosisen_HK
dc.subjectE prostanoid receptor 4en_HK
dc.subjectEP4 receptoren_HK
dc.subjectInflammationen_HK
dc.subject.meshBone Marrow Cells - metabolism - pathology-
dc.subject.meshBone Marrow Transplantation-
dc.subject.meshInflammation - metabolism - pathology-
dc.subject.meshPlaque, Atherosclerotic - genetics - metabolism - pathology-
dc.subject.meshReceptors, Prostaglandin E, EP4 Subtype - deficiency - genetics - metabolism-
dc.titleLack of EP4 receptors on bone marrow-derived cells enhances inflammation in atherosclerotic lesionsen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0008-6363&volume=89&issue=1&spage=234&epage=243&date=2011&atitle=Lack+of+EP4+receptors+on+bone+marrow-derived+cells+enhances+inflammation+in+atherosclerotic+lesions-
dc.identifier.emailTang, EHC: evatang1@hku.hken_HK
dc.identifier.authorityTang, EHC=rp01382en_HK
dc.description.naturelink_to_OA_fulltext-
dc.identifier.doi10.1093/cvr/cvq262en_HK
dc.identifier.pmid20736236-
dc.identifier.pmcidPMC3002867-
dc.identifier.scopuseid_2-s2.0-78650449351en_HK
dc.identifier.hkuros192144en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-78650449351&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume89en_HK
dc.identifier.issue1en_HK
dc.identifier.spage234en_HK
dc.identifier.epage243en_HK
dc.identifier.eissn1755-3245-
dc.identifier.isiWOS:000285416400028-
dc.publisher.placeUnited Kingdomen_HK
dc.identifier.scopusauthoridTang, EHC=9536518500en_HK
dc.identifier.scopusauthoridShimizu, K=35392936600en_HK
dc.identifier.scopusauthoridChristen, T=26535827400en_HK
dc.identifier.scopusauthoridRocha, VZ=23568679000en_HK
dc.identifier.scopusauthoridShvartz, E=36626245200en_HK
dc.identifier.scopusauthoridTesmenitsky, Y=36696899600en_HK
dc.identifier.scopusauthoridSukhova, G=35462921800en_HK
dc.identifier.scopusauthoridShi, GP=7402432834en_HK
dc.identifier.scopusauthoridLibby, P=7202591555en_HK

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