Article Text

PDF

P28 Glycomimetics: a novel approach to prevent vascular calcification
  1. FL Wilkinson1,
  2. GP Sidgwick1,
  3. P Walling1,
  4. A Shabbir1,
  5. R Weston1,
  6. AM Jones1,2,
  7. MY Alexander1,3
  1. 1Healthcare Science Research Centre, Manchester Metropolitan University, UK
  2. 2Division of Chemistry and Environmental Science, Manchester Metropolitan University, UK
  3. 3Cardiovascular Research Institute, University of Manchester, Manchester Academic Health Science Centre, UK

Abstract

The carbohydrate coating on all cell surfaces, called the glycocalyx, plays a key role in cellular communication, through variable structural changes. Glycomimetics represent a diverse array of small molecule heparan sulphate mimics, with the ability to target aberrant signalling and protein-protein interactions and the potential for an innovative therapy to resolve unmet needs in cardiovascular disease (CVD). Vascular calcification (VC) is a sinister complication in CVD and patients with diabetes, who have elevated glycated-low density lipoprotein (LDL) levels.

Our objective was to determine whether glycomimetics could inhibit VC in an in vitro human vascular smooth muscle cell (VSMCs) model.

VSMCs were incubated with calcification inducers β-glycerophosphate (5 mM) or glycated-LDL (10 µg/ml) or serum (5%) from patients with peripheral arterial disease, with or without four glycomimetics, and analysed for VC using alizarin red staining (AR), alkaline phosphatase activity (ALP) and ELISA. Glycomimetics significantly inhibited β-glycerophosphate-induced VC in VSMCs as demonstrated by AR, calcium deposition assay at day 21 and ALP activity at days 4, 7 and 10 (p < 0.01). Furthermore, VC was significantly increased by both glycated-LDL and patient serum compared to β-glycerophosphate (p < 0.05) at days 10 and 14 respectively. Glycomimetics inhibited both glycated-LDL and serum-induced VC as shown by reduced AR (p < 0.05), ALP activity at day 4 (p < 0.05) and the bone-related protein OCN.

We provide the first evidence that glycomimetics have the ability to protect against glycated-LDL and BGP-induced vascular calcification in vitro, and we are currently investigating the mechanism underlying this process for translation into an animal model of disease.

Statistics from Altmetric.com

Request permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.