Disease relevance of FGF2

• Using a model of chronic myocardial ischemia, animals were randomized to either treatment of the ischemic area by injections of adenovirus vector-FGF2 or no treatment [1].
• Selective pressure-regulated retroinfusion of fibroblast growth factor-2 into the coronary vein enhances regional myocardial blood flow and function in pigs with chronic myocardial ischemia [2].
• We have investigated the effects of intramyocardial delivery of FGF-2 in the presence and absence of heparin on angiogenesis in a porcine model of myocardial infarction [3].

High impact information on FGF2

• The prototype members of the heparin-binding fibroblast growth factor (FGF) family, acidic FGF (FGF-1) and basic FGF (FGF-2), are among the growth factors that act directly on vascular cells to induce endothelial cell growth and angiogenesis [4].
• Transfected cells produced significantly less perlecan than parent cells and showed a reduced ability to inhibit the binding and mitogenic activity of fibroblast growth factor-2 in vascular smooth muscle cells [5].
• GDNF signaling resulted in transcriptional upregulation of FGF-2, which in turn was found to support photoreceptor survival in an in vitro assay [6].
• Heparan sulfate (HS) regulates the kinetics of fibroblast growth factor 2 (FGF2)-stimulated intracellular signaling and differentially activates cell proliferation of cells expressing different FGF receptors (FGFRs) [7].
• Only the antithrombin-bound fraction of heparin competed with (3)H-heparin bound to FGFR in absence of FGF, whereas both antithrombin-bound and unretained fractions competed with radiolabeled heparin bound independently to FGF-1 and FGF-2 [8].

Chemical compound and disease context of FGF2

• CONCLUSIONS: Selective pressure-regulated retroinfusion increased tissue binding of FGF-2 and enhanced functionally relevant collateral perfusion compared with antegrade intracoronary delivery in pigs with chronic myocardial ischemia [2].

Biological context of FGF2

• Developmental and hormonal regulated gene expression of fibroblast growth factor 2 (FGF-2) and its receptors in porcine endometrium [9].
• Protein kinase C-dependent down-regulation of basic fibroblast growth factor (FGF-2) receptor by phorbol ester and epidermal growth factor in porcine granulosa cells [10].
• PDGF-AB induced a rapid MEK activation followed by phosphorylation of the MEK substrates ERK1/2 while FGF-2 showed a less pronounced and delayed activation [11].
• Transendocardial and transepicardial intramyocardial fibroblast growth factor-2 administration: myocardial and tissue distribution [12].
• RESULTS: Intracoronary 6-microg/kg FGF-2 increased angiographic collaterals (p = 0.046) and increased regional blood flow to the ischemic area from 0.36 +/- 0.07 to 0.59 +/- 0.08 mL/min/g at stress (vs control, p = 0.032) [13].

Anatomical context of FGF2

• The regulation of the basic fibroblast growth factor (bFGF, or FGF-2) receptor on porcine granulosa cells was studied [10].
• In the presence of FGF2 (20 ng/mL), the percentage of photoreceptor survival during the second week in culture was statistically significantly different, at least two times higher than in control experiments [14].
• Levels of natriuretic peptides were significantly decreased, and levels of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (FGF2) were significantly increased after BMI [15].
• CONCLUSIONS: The function of ischemic myocardium can be restored by a novel FGF2 gene delivery method using a gene-activated matrix [1].
• In a separate series of experiments porcine coronary arteries were chronically treated with FGF-2 itself in the same manner [16].

Associations of FGF2 with chemical compounds

• EB induced a significant suppression of FGF-2 mRNA, an effect which was antagonized by P and even prevented by P+EB [9].
• Phosphotyrosine immunoblots after stimulation of cultures with FGF2 and EGF revealed time-dependent appearance of multiple immunoreactive bands [14].
• Under these conditions, both inducers stimulated rapid activation of extracellular signal-regulated kinase (ERK2) at 5-10 min, a transient and lower intensity being induced by U46619 whereas that induced by FGF-2 was sustained (>1 h) [17].
• However, activation of ERK2 by FGF-2 was not affected by PGE2 whereas that of JNK1 by U46619 was inhibited, suggesting that inhibition of COX-2 expression by cAMP may be downstream of ERK2 [17].
• Short heparin sequences spaced by glycol-split uronate residues are antagonists of fibroblast growth factor 2 and angiogenesis inhibitors [18].

Regulatory relationships of FGF2

• In contrast, activation of Jun-N-terminal kinase (JNK1) was sustained with U46619 but poorly induced by FGF-2 [17].

Other interactions of FGF2

• The role of fibroblast growth factor-2 in the vascular effects of interleukin-1 beta in porcine coronary arteries in vivo [16].
• However, the reversibility of p27Kip1 down-regulation by UO126 was mainly observed after PDGF-AB stimulation, indicating MEK independent p27Kip1 down-regulation by FGF-2 [11].
• In single cells that migrated into the wound, fibroblast growth factor 2 and fibroblast growth factor receptor 1 were prominent [19].
• Seven weeks later, endothelium-dependent coronary microvascular responses to fibroblast growth factor-2 and vascular endothelial growth factor were assessed by videomicroscopy [20].
• Five groups of six animals received either D-methionine, sodium thiosulfate, fibroblast growth factor-2, brain-derived neurotrophic factor, or saline 0.9% [21].

Analytical, diagnostic and therapeutic context of FGF2

• Cell culture composition was characterized through the use of specific antibody markers of retinal neurons, and neuronal survival was quantified through viability assays as a function of time in the presence or absence of different doses of FGF2 and EGF [14].
• Western blot analysis of phosphotyrosine residues was used to monitor activation of FGF2 and EGF signaling pathways [14].
• The increased arteriogenesis as a result of FGF2 gene therapy leads to restoration of this myocardial function [1].
• Single intravenous infusion of FGF-2 was not effective in this model [13].
• Wounds were also fixed at 0, 2, and 24 hours and stained for fibroblast growth factor 2 and fibroblast growth factor receptor 1 by means of immunofluorescence and laser confocal microscopy [19].

References