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Heparin-independent mitogenicity in an endothelial and smooth muscle cell chimeric growth factor (S130K-HBGAM).
- Source :
-
American journal of surgery [Am J Surg] 2004 Nov; Vol. 188 (5), pp. 575-9. - Publication Year :
- 2004
-
Abstract
- Background: Through site-directed mutagenesis we have created a favorable fibroblast growth factor-1 (FGF-1) mutant (S130K) and linked it to a heparin-binding growth-associated molecule (HBGAM) to form the chimera S130K-HBGAM creating a heparin-independent, endothelial cell (EC)-specific mitogen.<br />Methods: The proliferative responses of primary canine carotid artery smooth muscle cells (SMC) and jugular vein EC to FGF-1, S130K, or S130K-HBGAM, with and without heparin (5 U/mL), was quantitated by measuring tritiated thymidine uptake over 24 hours and expressing the results as percent of positive control (20% fetal bovine serum [FBS]) for group comparison.<br />Results: Unlike FGF-1, both S130K and S130K-HBGAM are heparin-independent mitogens for EC and SMC. S130K-HBGAM was equivalent to FGF-1 with heparin at 6 nmol/L. S130K-HBGAM did not demonstrate relative EC specificity in this assay.<br />Conclusions: At higher concentrations, S130K-HBGAM is a potent, heparin-independent EC and SMC mitogen. Co-culture assays and in vivo delivery models may demonstrate EC specificity not identified in this single cell type proliferation assay.
- Subjects :
- Analysis of Variance
Animals
Base Sequence
Carotid Arteries cytology
Cell Proliferation drug effects
Cells, Cultured
Dogs
Endothelium, Vascular cytology
Endothelium, Vascular drug effects
Fibroblast Growth Factor 1 genetics
Models, Animal
Molecular Sequence Data
Muscle, Smooth, Vascular cytology
Muscle, Smooth, Vascular drug effects
Myocytes, Smooth Muscle drug effects
Point Mutation
Polymerase Chain Reaction
Probability
Recombinant Fusion Proteins genetics
Recombinant Fusion Proteins metabolism
Recombinant Proteins
Sensitivity and Specificity
Endothelium, Vascular metabolism
Fibroblast Growth Factor 1 metabolism
Fibroblast Growth Factor 1 pharmacology
Heparin pharmacology
Mitogens pharmacology
Muscle, Smooth, Vascular metabolism
Myocytes, Smooth Muscle metabolism
Recombinant Fusion Proteins pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 0002-9610
- Volume :
- 188
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- American journal of surgery
- Publication Type :
- Academic Journal
- Accession number :
- 15546573
- Full Text :
- https://doi.org/10.1016/j.amjsurg.2004.07.012