TY - JOUR
T1 - Reduced serum content and increased matrix stiffness promote the cardiac myofibroblast transition in 3D collagen matrices
AU - Galie, Peter A.
AU - Westfall, Margaret V.
AU - Stegemann, Jan P.
N1 - Funding Information:
This work was partially supported by a Microfluidics in Biomedical Sciences Training Program grant at the University of Michigan, sponsored by the National Institute of Biomedical Imaging and Bioengineering.
PY - 2011/11
Y1 - 2011/11
N2 - Introduction: The fibroblast-myofibroblast transition is an important event in the development of cardiac fibrosis and scar formation initiated after myocardial ischemia. The goals of the present study were to better understand the contribution of environmental factors to this transition and determine whether myofibroblasts provide equally important feedback to the surrounding environment. Methods: The influence of matrix stiffness and serum concentration on the myofibroblast transition was assessed by measuring message levels of a panel of cardiac fibroblast phenotype markers using quantitative reverse transcriptase polymerase chain reaction. Cell-mediated gel compaction measured the influence of environmental factors on cardiac fibroblast contractility. Immunohistochemistry characterized alpha-smooth muscle actin expression and cell morphology, while static and dynamic compression testing evaluated the effect of the cell response on the mechanical properties of the cell-seeded collagen hydrogels. Results: Both reduced serum content and increased matrix stiffness contributed to the myofibroblast transition, as indicated by contractile compaction of the gels, increased message levels of col3α1 and alpha-smooth muscle actin, and a less stellate morphology. However, the effects of serum and matrix stiffness were not additive. Mechanical testing indicated that reduced serum content increased the initial elastic modulus of cell-seeded gels and that gels lost their viscous character with time. Conclusions: The results suggest that reduced serum and increased matrix stiffness promote the myofibroblast phenotype in the myocardium. This transition both enhances and is promoted by matrix stiffness, indicating the presence of positive feedback that may contribute to the pathogenesis of cardiac fibrosis.
AB - Introduction: The fibroblast-myofibroblast transition is an important event in the development of cardiac fibrosis and scar formation initiated after myocardial ischemia. The goals of the present study were to better understand the contribution of environmental factors to this transition and determine whether myofibroblasts provide equally important feedback to the surrounding environment. Methods: The influence of matrix stiffness and serum concentration on the myofibroblast transition was assessed by measuring message levels of a panel of cardiac fibroblast phenotype markers using quantitative reverse transcriptase polymerase chain reaction. Cell-mediated gel compaction measured the influence of environmental factors on cardiac fibroblast contractility. Immunohistochemistry characterized alpha-smooth muscle actin expression and cell morphology, while static and dynamic compression testing evaluated the effect of the cell response on the mechanical properties of the cell-seeded collagen hydrogels. Results: Both reduced serum content and increased matrix stiffness contributed to the myofibroblast transition, as indicated by contractile compaction of the gels, increased message levels of col3α1 and alpha-smooth muscle actin, and a less stellate morphology. However, the effects of serum and matrix stiffness were not additive. Mechanical testing indicated that reduced serum content increased the initial elastic modulus of cell-seeded gels and that gels lost their viscous character with time. Conclusions: The results suggest that reduced serum and increased matrix stiffness promote the myofibroblast phenotype in the myocardium. This transition both enhances and is promoted by matrix stiffness, indicating the presence of positive feedback that may contribute to the pathogenesis of cardiac fibrosis.
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U2 - 10.1016/j.carpath.2010.10.001
DO - 10.1016/j.carpath.2010.10.001
M3 - Article
C2 - 21306921
AN - SCOPUS:79955407134
SN - 1054-8807
VL - 20
SP - 325
EP - 333
JO - Cardiovascular Pathology
JF - Cardiovascular Pathology
IS - 6
ER -