Fibroblast growth factor-1 prevents myocardial apoptosis triggered by ischemia reperfusion injury.
BACKGROUND
Apoptosis is a constant feature of reperfusion injury in ischemic cardiac myocytes, leading to late cell death. Since fibroblast growth factors (FGFs) inhibit apoptosis in differentiated cells, we hypothesized that FGF-1 (acidic FGF), in its native form, and a non-mitogenic isoform would attenuate myocardial ischemia-reperfusion- induced apoptosis.


RESULTS
The effect of native and non-mitogenic fibroblast growth factor-1 mutein (FGF-1 and m-FGF-1) on apoptosis assessed by terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) method was tested in a rat model of 20 min regional myocardial ischemia and 24h reperfusion. Myocardial ischemia followed by reperfusion resulted in a high myocardial apoptosis rate in the area at risk. When given as a systemic bolus inmediately after myocardial ischemia, both FGF-1 and m-FGF-1 significantly reduced apoptosis (by 60 and 61.2, respectively; p<0.0001).


CONCLUSIONS
The programed myocyte cell death triggered by ischemia-reperfusion injury is attenuated by FGF-1 in its native or non mitogenic isoforms, suggesting that this effect does not depend on the mitogenic properties of this protein. FGF-1 would contribute to the functional preservation of the myocardium after acute myocardial infarction.
Cuevas
P
P
Servicio de Histología, Hospital Ramón y Cajal Madrid, E-28034 Spain. pedro.cuevas@hrc.es
Reimers
D
D
Carceller
F
F
Martinez-Coso
V
V
Redondo-Horcajo
M
M
Saenz de Tejada
I
I
Giménez-Gallego
G
G
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects; D016220:Fibroblast Growth Factor 1 / Q000235:genetics / Q000494:pharmacology / Q000627:therapeutic use*; D006321:Heart / Q000187:drug effects; D006801:Humans; D007958:Leukocyte Count; D017202:Myocardial Ischemia / Q000473:pathology*; D015428:Myocardial Reperfusion Injury / Q000473:pathology / Q000517:prevention & control*; D009206:Myocardium / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000494:pharmacology
D011994:Recombinant Proteins; D016220:Fibroblast Growth Factor 1