Please use this identifier to cite or link to this item: https://doi.org/10.1007/s10456-018-9622-9
Title: Improved recovery from limb ischaemia by delivery of an affinity-isolated heparan sulphate
Authors: Poon, S
Lu, X
Smith, R.A.A
Ho, P 
Bhakoo, K 
Nurcombe, V
Cool, S.M 
Keywords: heparan sulfate
vasculotropin 165
heparan sulfate
affinity chromatography
angiogenesis
animal experiment
animal model
animal tissue
Article
blood volume
C57BL 6 mouse
controlled study
disease model
drug mechanism
hindlimb
histopathology
in vitro study
laser Doppler flowmetry
limb blood flow
limb injury
limb ischemia
limb perfusion
magnetic resonance angiography
male
mouse
musculoskeletal function
nonhuman
priority journal
protein blood level
protein degradation
protein isolation
protein stability
reperfusion
treatment response
vasculotropin 165 blood level
animal
chemistry
hindlimb
human
ischemia
isolation and purification
pathology
pathophysiology
RAW 264.7 cell line
umbilical vein endothelial cell
vascularization
Animals
Disease Models, Animal
Heparitin Sulfate
Hindlimb
Human Umbilical Vein Endothelial Cells
Humans
Ischemia
Mice
RAW 264.7 Cells
Issue Date: 2018
Publisher: Springer Netherlands
Citation: Poon, 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
Rights: Attribution 4.0 International
Abstract: Peripheral 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).
Source Title: Angiogenesis
URI: https://scholarbank.nus.edu.sg/handle/10635/179015
ISSN: 09696970
DOI: 10.1007/s10456-018-9622-9
Rights: Attribution 4.0 International
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