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Effects of heparin and heparin‐binding growth factor on human aortic adventitial fibroblasts (1012.4)
Author(s) -
Kalle Fanta,
Akins Robert
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.1012.4
Subject(s) - fibroblast growth factor , fibroblast , heparin , medicine , growth factor , pathology , microbiology and biotechnology , in vitro , chemistry , biology , biochemistry , receptor
Cardiovascular diseases are primary treated using bypass graft surgery and angioplasty; unfortunately, these procedures often fail due to maladaptive tissue remodeling leading to stenosis, fibrosis, and vessel failure. Methods to decrease failure rates are needed. We are developing instructive biomaterials for placement along the abluminal surface of at‐risk vessels to provide mechanical support and to deliver bioactive molecules and/or stem cells to help attenuate maladaptive responses, encourage healing, and improve clinical outcomes. The present study examines the effects of critical biomaterial components including basic fibroblast growth factor (FGF2), low‐molecular weight heparin (LMWH) and desulfated LMWH on vascular cells. Cell morphology, proliferation, and viability are assessed using fluorescence microscopy. Image Pro and SPSS software packages are used to acquire and analyze data. Data indicate that FGF2 and LMWH affect human aortic adventitial fibroblast (AoAF) phenotype. The presence of FGF2 significantly increased proliferation rates and the appearance of filopodia; whereas, the absence of FGF2 was associated with an increase in the prevalence of lamellipodia and stress fibers. Increasing LMWH doses correlated with decreased AoAF proliferation and alterations in cell morphology. Desulfated LMWH did not alter FGF2‐mediated effects on cell phenotype. These data suggest that the biomaterial components LMWH and FGF2 can influence the phenotype of cardiovascular cells like AoAFs. Although in vivo, LMWH is thought to potentiate FGF2‐induced effects, in our system, LMWH significantly decreased AoAF proliferation, particularly in the absence of FGF2. The sulfation state of LMWH was critical to these effects. Further studies to determine the mechanisms accounting for these effects and to establish combined effects on cell phenotype will be needed to enable development of injectable formulations that may be useful in improving clinical outcome. Grant Funding Source : supported by the Delaware INBRE program with a grant from the National Institute of General Medical