Effects of Diabetes on Matrix Protein Expression and Response to Cyclic Strain by Cardiac Fibroblasts

Abstract

Overcoming the effects of hyperglycemic conditions on matrix remodeling by cardiac fibroblasts represents a novel therapeutic approach to stimulate regeneration of cardiac tissue in the context of diabetes. The purpose of this study was to investigate the effects of diabetic conditions on the extracellular matrix (ECM) protein expression and biomechanical response of cardiac fibroblasts. Two types of diabetic conditions were used: in vivo using rat model of diabetic cardiomyopathy (DCM), or in vitro using high glucose culture medium. A commercially available Flexcell system was used to apply uniaxial stretch to rat cardiac fibroblasts, and cell response was assessed, including MMP-2 (ECM remodeling), collagen I (ECM deposition), and vascular endothelial growth factor (cell migration stimulus) expression as well as fibroblast morphology, orientation, proliferation and apoptosis. The results demonstrate differential cell responses to the two models of diabetic condition. Cardiac fibroblasts from the in vivo rat model of DCM exhibited an overall reduced synthetic activity and proliferation, while high glucose conditions lead to apparent increases in cell responses. In the in vivo rat model, exposure to cyclic strain appeared to act toward restoration of cell proliferation and collagen I expression that were decreased with diabetes.