Improved recovery from limb ischaemia by delivery of an affinity-isolated heparan sulphate

Angiogenesis
Selina PoonSimon M Cool

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...Continue Reading

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Citations

Aug 11, 2020·Stroke; a Journal of Cerebral Circulation·Su Jing ChanVictor Nurcombe
Feb 28, 2019·Journal of Materials Chemistry. B, Materials for Biology and Medicine·Chao HeChangsheng Zhao
Oct 3, 2020·Bioactive Materials·Cui LiXiaowei Li
Dec 18, 2020·Frontiers in Cell and Developmental Biology·Maanasa RavikumarSimon M Cool
Apr 16, 2021·Advanced Science·Grazia MarsicoAbhay Pandit
Nov 28, 2018·ACS Chemical Biology·Olga V ZubkovaJeremy E Turnbull

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Methods Mentioned

BETA
surgical bypass
Protein Assay
chip
surface-plasmon resonance
affinity capture

Software Mentioned

PIMSoft
GraphPad Prism
Metafer
ImageStudio Lite
GraphPad
ImageJ

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