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42 Glycation and vascular calcification: developing an anti-calcification strategy
  1. R Weston1,
  2. GP Sidgwick1,
  3. N Ahmed1,
  4. N Nazhad1,
  5. A Schiro2,3,
  6. F Serracino Inglott1,2,3,
  7. FL Wilkinson1,
  8. MY Alexander1,2
  1. 1Healthcare Science Research Centre, Manchester Metropolitan University, Chester Street, Manchester, M1 5GD, UK
  2. 2Cardiovascular Research Institute, University of Manchester, Grafton St, Manchester, UK
  3. 3Vascular Unit, Central Manchester NHS Trust, Manchester Academic Health Science Centre, Manchester, UK

Abstract

It is well established that vascular calcification is a common complication in diabetes and recent studies suggest that glycation may play a pathogenic role in this process. The aim of this study was to investigate the role of glycation in the induction of calcification in vascular smooth muscle cells (SMCs), and the potential inhibitory effects of the anti-diabetic agent, Momordica Charantia. Vascular SMCs were incubated with native or glycated LDL in the presence of osteogenic media and mineral deposition was determined using alizarin red staining and alkaline phosphatase (ALP) activity. We found that SMCs incubated in osteogenic media exhibited mineralisation after 7 days. This calcification was significantly increased following treatment with glycated-LDL, but not by native LDL. Furthermore, we found that ALP activity was significantly elevated at day 4 in glycated-LDL treated cells, compared to those incubated in native LDL. The vascular SMCs were exposed to increasing concentrations of Momordica Charantia extract in the presence of osteogenic media. ALP activity was reduced in treated cells, compared to osteogenic controls. Furthermore, we found that Momordica Charantia reduced gene expression of a range of biomarkers linked with vascular calcification after 4 days in a dose-dependent manner, including osteocalcin and BMP-2. In conclusion, we have shown that glycated LDL promotes osteogenic differentiation of vascular SMCs. Momordica Charantia extract shows promise as a potential therapeutic agent to reduce vascular calcification. Future work will identify the active ingredient responsible for calcification inhibitory effects, and establish whether it links to the pathological glycation-induced osteogenesis.

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