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Intracoronary administration of FGF-2: a computational model of myocardial deposition and retention.
| Content Provider | Semantic Scholar |
|---|---|
| Copyright Year | 2005 |
| Abstract | This study uses a computational model to characterize the myocardial deposition and retention of basic fibroblast growth factor (FGF-2) at the cellular level after intracoronary (IC) administration of exogenous FGF-2. The model is applied to the in situ conditions present within the myocardium of a dog for which the plasma pharmacokinetics resulting from IC injection of FGF-2 were recorded. Our estimates show that the processes involved in FGF-2 signaling are not diffusion limited; rather, the response time is determined by the reaction time of FGF-2 binding to cell surface receptors. Additionally, the processes of receptor secretion and internalization are found to play crucial roles in the FGF-2 dynamics; future experiments are required to quantify these processes. The model predictions obtained in this study suggest that IC administration of FGF-2 via either a single bolus or repetitive injections causes a transient increase (time scale of hours) in myocardial FGF-2 concentration if the endogenous level of free interstitial FGF-2 is low enough to allow permeation of FGF-2 molecules from the microvascular to the interstitial spaces. The model shows that the majority (64%) of the extracellular FGF-2 ligands are located within the interstitium, and similar fractions are found in the basement membrane and extracellular matrix. Among the FGF-2 molecules found within the interstitium, 2% are free and 98% are bound to interstitial heparan sulfate proteoglycans. These results support the theory of extracellular control of the bioavailability of FGF-2 via dynamic storage of FGF-2 within the basement membrane and extracellular matrix. |
| File Format | PDF HTM / HTML |
| Alternate Webpage(s) | http://ajpheart.physiology.org/content/ajpheart/288/1/H263.full.pdf |
| Alternate Webpage(s) | http://pages.jh.edu/~apopel/Articles/Fillion_2005_IntracoronaryAdministrationFGF2.pdf |
| PubMed reference number | 15331374v1 |
| Volume Number | 288 |
| Issue Number | 1 |
| Journal | American journal of physiology. Heart and circulatory physiology |
| Language | English |
| Access Restriction | Open |
| Subject Keyword | Basement membrane Estimated Extracellular Matrix Fibroblast Growth Factor 2 Heparan Sulfate Proteoglycans Heparitin Sulfate Ligands Myocardium Proteoglycan |
| Content Type | Text |
| Resource Type | Article |
