Please use this identifier to cite or link to this item: https://doi.org/10.1007/s10456-018-9622-9
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dc.titleImproved recovery from limb ischaemia by delivery of an affinity-isolated heparan sulphate
dc.contributor.authorPoon, S
dc.contributor.authorLu, X
dc.contributor.authorSmith, R.A.A
dc.contributor.authorHo, P
dc.contributor.authorBhakoo, K
dc.contributor.authorNurcombe, V
dc.contributor.authorCool, S.M
dc.date.accessioned2020-10-22T07:18:32Z
dc.date.available2020-10-22T07:18:32Z
dc.date.issued2018
dc.identifier.citationPoon, S, Lu, X, Smith, R.A.A, Ho, P, Bhakoo, K, Nurcombe, V, Cool, S.M (2018). Improved recovery from limb ischaemia by delivery of an affinity-isolated heparan sulphate. Angiogenesis 21 (4) : 777-791. ScholarBank@NUS Repository. https://doi.org/10.1007/s10456-018-9622-9
dc.identifier.issn09696970
dc.identifier.urihttps://scholarbank.nus.edu.sg/handle/10635/179015
dc.description.abstractPeripheral arterial disease is a major cause of limb loss and its prevalence is increasing worldwide. As most standard-of-care therapies yield only unsatisfactory outcomes, more options are needed. Recent cell- and molecular-based therapies that have aimed to modulate vascular endothelial growth factor-165 (VEGF165) levels have not yet been approved for clinical use due to their uncertain side effects. We have previously reported a heparan sulphate (termed HS7) tuned to avidly bind VEGF165. Here, we investigated the ability of HS7 to promote vascular recovery in a murine hindlimb vascular ischaemia model. HS7 stabilised VEGF165 against thermal and enzyme degradation in vitro, and isolated VEGF165 from serum via affinity-chromatography. C57BL6 mice subjected to unilateral hindlimb ischaemia injury received daily intramuscular injections of respective treatments (n = 8) and were assessed over 3 weeks by laser Doppler perfusion, magnetic resonance angiography, histology and the regain of function. Mice receiving HS7 showed improved blood reperfusion in the footpad by day 7. In addition, they recovered hindlimb blood volume two- to fourfold faster compared to the saline group; the greatest rate of recovery was observed in the first week. Notably, 17% of HS7-treated animals recovered full hindlimb function by day 7, a number that grew to 58% and 100% by days 14 and 21, respectively. This was in contrast to only 38% in the control animals. These results highlight the potential of purified glycosaminoglycan fractions for clinical use following vascular insult, and confirm the importance of harnessing the activity of endogenous pro-healing factors generated at injury sites. © 2018, The Author(s).
dc.publisherSpringer Netherlands
dc.rightsAttribution 4.0 International
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.sourceUnpaywall 20201031
dc.subjectheparan sulfate
dc.subjectvasculotropin 165
dc.subjectheparan sulfate
dc.subjectaffinity chromatography
dc.subjectangiogenesis
dc.subjectanimal experiment
dc.subjectanimal model
dc.subjectanimal tissue
dc.subjectArticle
dc.subjectblood volume
dc.subjectC57BL 6 mouse
dc.subjectcontrolled study
dc.subjectdisease model
dc.subjectdrug mechanism
dc.subjecthindlimb
dc.subjecthistopathology
dc.subjectin vitro study
dc.subjectlaser Doppler flowmetry
dc.subjectlimb blood flow
dc.subjectlimb injury
dc.subjectlimb ischemia
dc.subjectlimb perfusion
dc.subjectmagnetic resonance angiography
dc.subjectmale
dc.subjectmouse
dc.subjectmusculoskeletal function
dc.subjectnonhuman
dc.subjectpriority journal
dc.subjectprotein blood level
dc.subjectprotein degradation
dc.subjectprotein isolation
dc.subjectprotein stability
dc.subjectreperfusion
dc.subjecttreatment response
dc.subjectvasculotropin 165 blood level
dc.subjectanimal
dc.subjectchemistry
dc.subjecthindlimb
dc.subjecthuman
dc.subjectischemia
dc.subjectisolation and purification
dc.subjectpathology
dc.subjectpathophysiology
dc.subjectRAW 264.7 cell line
dc.subjectumbilical vein endothelial cell
dc.subjectvascularization
dc.subjectAnimals
dc.subjectDisease Models, Animal
dc.subjectHeparitin Sulfate
dc.subjectHindlimb
dc.subjectHuman Umbilical Vein Endothelial Cells
dc.subjectHumans
dc.subjectIschemia
dc.subjectMice
dc.subjectRAW 264.7 Cells
dc.typeArticle
dc.contributor.departmentORTHOPAEDIC SURGERY
dc.contributor.departmentSURGERY
dc.description.doi10.1007/s10456-018-9622-9
dc.description.sourcetitleAngiogenesis
dc.description.volume21
dc.description.issue4
dc.description.page777-791
dc.published.statePublished
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