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Molecular Imaging of Platelet-Endothelial Interactions and Endothelial von Willebrand Factor in Early and Mid-Stage Atherosclerosis

DC FieldValueLanguage
dc.contributor.author심지영-
dc.date.accessioned2016-02-04T11:38:09Z-
dc.date.available2016-02-04T11:38:09Z-
dc.date.issued2015-
dc.identifier.issn1941-9651-
dc.identifier.urihttps://ir.ymlib.yonsei.ac.kr/handle/22282913/140861-
dc.description.abstractBACKGROUND: Nonthrombotic platelet-endothelial interactions may contribute to atherosclerotic plaque development, although in vivo studies examining mechanism without platelet preactivation are lacking. Using in vivo molecular imaging at various stages of atherosclerosis, we quantified platelet-endothelial interactions and evaluated the contribution of major adhesion pathways. METHODS AND RESULTS: Mice deficient for the low-density lipoprotein receptor and Apobec-1 were studied as an age-dependent model of atherosclerosis at 10, 20, 30, and 40 weeks of age, which provided progressive increase in stage from early fatty streak (10 weeks) to large complex plaques without rupture (40 weeks). Platelet-targeted contrast ultrasound molecular imaging of the thoracic aorta performed with microbubbles targeted to GPIbα demonstrated selective signal enhancement as early as 10 weeks of age. This signal increased progressively with age (almost 8-fold increase from 10 to 40 weeks, analysis of variance P<0.001). Specificity for platelet targeting was confirmed by the reduction in platelet-targeted signal commensurate with the decrease in platelet count after immunodepletion with anti-GPIb or anti-CD41 antibody. Inhibition of P-selectin in 20 and 40 weeks atherosclerotic mice resulted in a small (15% to 30%) reduction in platelet signal. Molecular imaging with microbubbles targeted to the A1 domain of von Willebrand factor demonstrated selective signal enhancement at all time points, which did not significantly increase with age. Treatment of 20 and 40 week mice with recombinant ADAMTS13 eliminated platelet and von Willebrand factor molecular imaging signal. CONCLUSIONS: Platelet-endothelial interactions occur in early atherosclerosis. These interactions are in part caused by endothelial von Willebrand factor large multimers, which can be reversed with exogenous ADAMTS13.-
dc.description.statementOfResponsibilityopen-
dc.relation.isPartOfCIRCULATION-CARDIOVASCULAR IMAGING-
dc.rightsCC BY-NC-ND 2.0 KR-
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/2.0/kr/-
dc.subject.MESHADAM Proteins/metabolism-
dc.subject.MESHADAMTS13 Protein-
dc.subject.MESHAPOBEC-1 Deaminase-
dc.subject.MESHAnimals-
dc.subject.MESHAorta, Thoracic/diagnostic imaging-
dc.subject.MESHAorta, Thoracic/metabolism*-
dc.subject.MESHAortic Diseases/diagnostic imaging-
dc.subject.MESHAortic Diseases/genetics-
dc.subject.MESHAortic Diseases/metabolism*-
dc.subject.MESHAtherosclerosis/diagnostic imaging-
dc.subject.MESHAtherosclerosis/genetics-
dc.subject.MESHAtherosclerosis/metabolism*-
dc.subject.MESHBlood Platelets/diagnostic imaging-
dc.subject.MESHBlood Platelets/metabolism*-
dc.subject.MESHContrast Media-
dc.subject.MESHCytidine Deaminase/deficiency-
dc.subject.MESHCytidine Deaminase/genetics-
dc.subject.MESHDisease Models, Animal-
dc.subject.MESHEndothelial Cells/diagnostic imaging-
dc.subject.MESHEndothelial Cells/metabolism*-
dc.subject.MESHMice, Inbred C57BL-
dc.subject.MESHMice, Knockout-
dc.subject.MESHMicrobubbles-
dc.subject.MESHMicroscopy, Fluorescence-
dc.subject.MESHMolecular Imaging/methods*-
dc.subject.MESHP-Selectin/metabolism-
dc.subject.MESHPlatelet Adhesiveness*-
dc.subject.MESHPlatelet Glycoprotein GPIb-IX Complex/metabolism-
dc.subject.MESHProtein Multimerization-
dc.subject.MESHReceptors, LDL/deficiency-
dc.subject.MESHReceptors, LDL/genetics-
dc.subject.MESHTime Factors-
dc.subject.MESHUltrasonography-
dc.subject.MESHvon Willebrand Factor/metabolism*-
dc.titleMolecular Imaging of Platelet-Endothelial Interactions and Endothelial von Willebrand Factor in Early and Mid-Stage Atherosclerosis-
dc.typeArticle-
dc.contributor.collegeCollege of Medicine (의과대학)-
dc.contributor.departmentDept. of Internal Medicine (내과학)-
dc.contributor.googleauthorChi Young Shim-
dc.contributor.googleauthorYa Ni Liu-
dc.contributor.googleauthorTamara Atkinson-
dc.contributor.googleauthorAris Xie-
dc.contributor.googleauthorTed Foster-
dc.contributor.googleauthorBrian P. Davidson-
dc.contributor.googleauthorMackenzie Treible-
dc.contributor.googleauthorYue Qi-
dc.contributor.googleauthorJosé A. López-
dc.contributor.googleauthorAdam Munday-
dc.contributor.googleauthorZaverio Ruggeri-
dc.contributor.googleauthorJonathan R. Lindner-
dc.identifier.doi10.1161/CIRCIMAGING.114.002765-
dc.admin.authorfalse-
dc.admin.mappingfalse-
dc.contributor.localIdA02213-
dc.relation.journalcodeJ00538-
dc.identifier.eissn1942-0080-
dc.identifier.pmid26156014-
dc.identifier.urlhttp://circimaging.ahajournals.org/content/8/7/e002765.long-
dc.subject.keywordatherosclerosis-
dc.subject.keywordmolecular imaging-
dc.subject.keywordplatelet-
dc.subject.keywordvon Willebrand factor-
dc.contributor.alternativeNameShim, Chi Young-
dc.contributor.affiliatedAuthorShim, Chi Young-
dc.rights.accessRightsnot free-
dc.citation.volume8-
dc.citation.number7-
dc.citation.startPage002765-
dc.identifier.bibliographicCitationCIRCULATION-CARDIOVASCULAR IMAGING, Vol.8(7) : 002765, 2015-
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers

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