Vaccinia Virus Complement Control Protein Diminishes Formation of Atherosclerotic Lesions: Complement Is Centrally Involved in Atherosclerotic Disease

2.50
Hdl Handle:
http://hdl.handle.net/2336/2853
Title:
Vaccinia Virus Complement Control Protein Diminishes Formation of Atherosclerotic Lesions: Complement Is Centrally Involved in Atherosclerotic Disease
Authors:
Thorbjornsdottir, Perla; Kolka, Ragnhildur; Gunnarsson, Eggert; Bambir, Slavko H; Thorgeirsson, Gudmundur; Kotwal, Girish J; Arason, Guðmundur J
Citation:
Ann N Y Acad Sci 2005, 1056:1-15
Issue Date:
2005
Abstract:
Complement is known to be activated in atherosclerotic lesions, but the importance of this event in disease pathology is a matter of debate. Studies of rabbits fed a high-fat diet have indicated complement activation as a rate-limiting step, whereas results from genetically modified mouse strains (ApoE(-/-) or LDLR(-/-)) have failed to support this finding. To resolve whether this reflects differences between species or between genetically driven and diet-induced disease, we studied the effect of a complement inhibitor, vaccinia virus complement control protein (VCP), on C57BL/6 mice, the background strain of ApoE(-/-) and LDLR(-/-) mice. Atherosclerosis was induced by a high-fat diet, and VCP (20 mg/kg) was injected once per week after the eighth week. Fatty streak development was monitored at 15 weeks by microscopic examination of oil red-O-stained sections from the root of the aorta. VCP injections led to significant (50%) reduction of lesion size (P = 0.004). Lesions were marked by gradual accumulation of lipids and macrophages but did not develop beyond the fatty streak stage. VCP activity disappeared from serum in 4 days, and the possibility therefore exists that a higher level of protection may be achieved by more frequent injections. We conclude that the development of fatty streaks in diet-induced atherosclerotic disease can be significantly retarded by prophylactic treatment with a complement inhibitor. These results support previous findings from complement-deficient rabbits and suggest that the pathogenesis of atherosclerosis in diet-induced disease differs from that induced by major defects in lipid metabolism.
Description:
To access publisher full text version of this article. Please click on the hyperlink in Additional Links field
Additional Links:
http://dx.doi.org/10.1196/annals.1352.001

Full metadata record

DC FieldValue Language
dc.contributor.authorThorbjornsdottir, Perla-
dc.contributor.authorKolka, Ragnhildur-
dc.contributor.authorGunnarsson, Eggert-
dc.contributor.authorBambir, Slavko H-
dc.contributor.authorThorgeirsson, Gudmundur-
dc.contributor.authorKotwal, Girish J-
dc.contributor.authorArason, Guðmundur J-
dc.date.accessioned2006-05-18T15:35:07Z-
dc.date.available2006-05-18T15:35:07Z-
dc.date.issued2005-
dc.identifier.citationAnn N Y Acad Sci 2005, 1056:1-15en
dc.identifier.issn0077-8923-
dc.identifier.pmid16387673-
dc.identifier.doi10.1196/annals.1352.001-
dc.identifier.urihttp://hdl.handle.net/2336/2853-
dc.descriptionTo access publisher full text version of this article. Please click on the hyperlink in Additional Links fielden
dc.description.abstractComplement is known to be activated in atherosclerotic lesions, but the importance of this event in disease pathology is a matter of debate. Studies of rabbits fed a high-fat diet have indicated complement activation as a rate-limiting step, whereas results from genetically modified mouse strains (ApoE(-/-) or LDLR(-/-)) have failed to support this finding. To resolve whether this reflects differences between species or between genetically driven and diet-induced disease, we studied the effect of a complement inhibitor, vaccinia virus complement control protein (VCP), on C57BL/6 mice, the background strain of ApoE(-/-) and LDLR(-/-) mice. Atherosclerosis was induced by a high-fat diet, and VCP (20 mg/kg) was injected once per week after the eighth week. Fatty streak development was monitored at 15 weeks by microscopic examination of oil red-O-stained sections from the root of the aorta. VCP injections led to significant (50%) reduction of lesion size (P = 0.004). Lesions were marked by gradual accumulation of lipids and macrophages but did not develop beyond the fatty streak stage. VCP activity disappeared from serum in 4 days, and the possibility therefore exists that a higher level of protection may be achieved by more frequent injections. We conclude that the development of fatty streaks in diet-induced atherosclerotic disease can be significantly retarded by prophylactic treatment with a complement inhibitor. These results support previous findings from complement-deficient rabbits and suggest that the pathogenesis of atherosclerosis in diet-induced disease differs from that induced by major defects in lipid metabolism.en
dc.language.isoenen
dc.publisherNew York Academy of Sciencesen
dc.relation.urlhttp://dx.doi.org/10.1196/annals.1352.001en
dc.subject.meshAtherosclerosisen
dc.subject.meshComplement Activationen
dc.subject.meshComplement System Proteinsen
dc.subject.meshVaccinia virusen
dc.subject.meshViral Proteinsen
dc.titleVaccinia Virus Complement Control Protein Diminishes Formation of Atherosclerotic Lesions: Complement Is Centrally Involved in Atherosclerotic Diseaseen
dc.typeArticleen
dc.identifier.journalAnnals of the New York Academy of Sciencesen
dc.format.digYES-

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