Calcium dobesilate may alleviate diabetes‑induced endothelial dysfunction and inflammation

Mol Med Rep. 2017 Dec;16(6):8635-8642. doi: 10.3892/mmr.2017.7740. Epub 2017 Oct 9.


Diabetic kidney disease (DKD) is a leading cause of end‑stage renal disease. However, the pathogenesis of DKD remains unclear, and no effective treatments for the disease are available. Thus, there is an urgent need to elucidate the pathogenic mechanisms of DKD and to develop more effective therapies for this disease. Human umbilical vein endothelial cells (HUVECs) were cultured using different D‑glucose concentrations to determine the effect of high glucose (HG) on the cells. Alternatively, HUVECs were incubated with 100 µmol/l calcium dobesilate (CaD) to detect its effects. The authors subsequently measured HUVEC proliferation via cell counting kit‑8 assays. In addition, HUVEC angiogenesis was investigated via migration assays and fluorescein isothiocyanate (FITC)‑labelled bovine serum albumin (BSA) permeability assays. The content or distribution of markers of endothelial dysfunction [vascular endothelial growth factor (VEGF), VEGF receptor (R) and endocan) or inflammation [intercellular adhesion molecule (ICAM)‑1, monocyte chemotactic protein (MCP)‑1 and pentraxin‑related protein (PTX3)] was evaluated via reverse transcription‑quantitative polymerase chain reaction and western blotting. HG treatment induced increased in VEGF, VEGFR, endocan, ICAM‑1, MCP‑1 and PTX3 mRNA and protein expression in HUVECs. HG treatment for 24 to 48 h increased cell proliferation in a time‑dependent manner, but the cell proliferation rate was decreased at 72 h of HG treatment. Conversely, CaD inhibited abnormal cell proliferation. HG treatment also significantly enhanced HVUEC migration compared to the control treatment. In contrast, CaD treatment partially inhibited HUVEC migration compared to HG exposure. HG‑treated HUVECs exhibited increased FITC‑BSA permeability compared to control cells cultured in medium alone; however, CaD application prevented the HG‑induced increase in FITC‑BSA permeability and suppressed HG‑induced overexpression of endothelial markers (VEGF, VEGFR‑2, endocan) and inflammation markers (ICAM‑1, MCP‑1, PTX3) in HUVECs. CaD has angioprotective properties and protects endothelial cells partly by ameliorating HG‑induced inflammation. The current results demonstrated the potential applicability of CaD to the treatment of diabetic nephropathy, particularly during the early stages of this disease.

MeSH terms

  • Biomarkers / metabolism
  • C-Reactive Protein / metabolism
  • Calcium Dobesilate / pharmacology
  • Calcium Dobesilate / therapeutic use*
  • Cell Membrane Permeability / drug effects
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Chemokine CCL2 / metabolism
  • Diabetes Mellitus / drug therapy*
  • Diabetes Mellitus / pathology
  • Diabetes Mellitus / physiopathology*
  • Endothelium, Vascular / drug effects
  • Endothelium, Vascular / pathology*
  • Endothelium, Vascular / physiopathology*
  • Glucose / toxicity
  • Human Umbilical Vein Endothelial Cells / drug effects
  • Human Umbilical Vein Endothelial Cells / metabolism
  • Humans
  • Inflammation / pathology*
  • Inflammation Mediators / metabolism
  • Intercellular Adhesion Molecule-1 / metabolism
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / metabolism
  • Proteoglycans / genetics
  • Proteoglycans / metabolism
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Serum Amyloid P-Component / metabolism
  • Time Factors
  • Up-Regulation / drug effects
  • Vascular Endothelial Growth Factor A / genetics
  • Vascular Endothelial Growth Factor A / metabolism
  • Vascular Endothelial Growth Factor Receptor-2 / genetics
  • Vascular Endothelial Growth Factor Receptor-2 / metabolism


  • Biomarkers
  • Chemokine CCL2
  • ESM1 protein, human
  • Inflammation Mediators
  • Neoplasm Proteins
  • Proteoglycans
  • RNA, Messenger
  • Serum Amyloid P-Component
  • Vascular Endothelial Growth Factor A
  • Intercellular Adhesion Molecule-1
  • PTX3 protein
  • Calcium Dobesilate
  • C-Reactive Protein
  • Vascular Endothelial Growth Factor Receptor-2
  • Glucose