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Glycated albumin modulates endothelial cell thrombogenic and inflammatory responses

David A Rubenstein1, Zahra Maria, Wei Yin

  • 1School of Mechanical and Aerospace Engineering, Oklahoma State University, Stillwater, Oklahoma, USA. david.rubenstein@okstate.edu

Journal of Diabetes Science and Technology
|July 5, 2011
PubMed

Insights

Advanced glycation end products (AGEs) in diabetes damage endothelial cells, increasing their procoagulant and inflammatory potential. This AGEs-induced endothelial dysfunction may drive platelet activation in diabetic cardiovascular disease.

Area of Science:

  • Vascular biology
  • Diabetic complications
  • Cardiovascular disease

Background:

  • Diabetic vasculature contributes to cardiovascular disease via endothelial cell and platelet dysfunction.
  • Advanced glycation end products (AGEs) are implicated in inducing these cellular changes.
  • The specific impact of AGEs on endothelial cell thrombogenicity and inflammation remains undercharacterized.

Purpose of the Study:

  • To investigate the effects of AGEs on endothelial cell thrombogenicity and inflammatory responses.
  • To evaluate changes in endothelial cell viability, density, morphology, and metabolic activity upon AGEs exposure.

Main Methods:

  • Chemical modification of albumin with glucose to create glycated albumin.
  • Exposure of endothelial cells to glycated albumin in a cell culture system for up to 5 days.
  • Assessment of endothelial cell viability, proliferation, metabolic activity, and surface marker expression (ICAM-1, thrombomodulin, tissue factor, connexin-43, caveolin-1).

Main Results:

  • Endothelial cells exposed to irreversibly glycated albumin exhibited reduced viability, slower proliferation, and decreased metabolic activity.
  • Exposure to glycated albumin rendered endothelial cells procoagulant and proinflammatory.
  • No significant trends were observed in the expression of connexin-43 or caveolin-1.

Conclusions:

  • Irreversibly glycated albumin is detrimental to endothelial cells, promoting procoagulant and inflammatory characteristics.
  • AGEs-induced endothelial cell activation may precede and contribute to platelet activation in diabetic conditions.
  • These findings highlight a potential mechanism for AGEs in diabetic cardiovascular pathology.
Abstract

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