Effects of elevated glucose levels on interactions of cardiac fibroblasts with the extracellular matrix

  • Xiaoyi Zhang
  • James A. StewartJr.
  • Ian D. Kane
  • Erin P. Massey
  • Dawn O. Cashatt
  • Wayne E. Carver
Article
First Online:
Received:
Accepted:

Abstract

Exposure of fibroblasts to high glucose levels promotes a fibrotic response characterized by increased expression of extracellular matrix components including interstitial collagens. Little is known about the effects of glucose levels on other aspects of fibroblast function. Fibroblasts in the myocardium are surrounded by an extensive extracellular matrix composed predominantly of type I collagen. Interactions between fibroblasts and the myocardial extracellular matrix are thought to affect heart function by altering ventricular diastolic properties. The purpose of the present study was to determine the effects of elevated glucose levels on the interactions between heart fibroblasts and the collagenous extracellular matrix. Studies were performed to determine the effects of relative glucose levels on the ability of fibroblasts to migrate on and contract a three-dimensional collagenous substratum. These experiments illustrated that exposure of cardiac fibroblasts to high glucose levels (25 mM) resulted in decreased migratory activity of fibroblasts on a collagen matrix and decreased fibroblast proliferation. In addition, high glucose stimulated collagen and collagen-binding integrin expression and contraction of three-dimensional collagen gels by cardiac fibroblasts. These studies illustrate that altered glucose levels induce important changes in the interactions of cardiac fibroblasts with the collagenous extracellular matrix.

Keywords

Fibroblast Integrin Glucose Fibrosis Collagen Migration 
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Notes

Acknowledgements

The authors would like to thank Cheryl Cook for assistance in the isolation and culture of heart fibroblasts for these studies. This work was supported by National Institutes of Health grants HL 65441 and HL 62228 (WEC).

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Copyright information

© The Society for In Vitro Biology 2007

Authors and Affiliations

  • Xiaoyi Zhang
    • 1
  • James A. StewartJr.
    • 1
  • Ian D. Kane
    • 1
  • Erin P. Massey
    • 1
  • Dawn O. Cashatt
    • 1
  • Wayne E. Carver
    • 1
  1. 1.Department of Cell and Developmental Biology and AnatomyUniversity of South Carolina School of MedicineColumbiaUSA

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