High- but not low-molecular weight FGF-2 causes cardiac hypertrophy in vivo; possible involvement of cardiotrophin-1.
The heart expresses high and low molecular weight (hmw, lmw) fibroblast growth factor 2 (FGF-2) isoforms. While the injury-repair-related activities of lmw-FGF-2 have been studied extensively, those of hmw-FGF-2 have not. Thus, we investigated the effects of hmw-FGF-2 on acute as well as chronic responses to myocardial infarction (MI) induced by irreversible coronary occlusion in the rat. Hmw- or lmw-FGF-2 was injected into the ischemic zone during acute evolving MI. Both isoforms were equally effective in reducing infarct size (at 24 h post-MI) and improving heart function up to 6 weeks post-MI, compared to a vehicle-treated infarcted group. Lmw-FGF-2 alone upregulated vascularization in the infarct. Hmw-FGF-2 elicited significant hypertrophy, compared to the vehicle-treated group, at 4-8 weeks post-MI, assessed by ultrasound, heart morphometry and cardiomyocyte cross-sectional area. In addition, hmw- (but not lmw-) FGF-2-treated hearts displayed increased accumulation of the cytokine cardiotrophin-1 and its signal transducer gp130. In culture, hmw- (but not lmw-) FGF-2 increased cardiomyocyte protein synthesis and cell size as well as upregulated cardiotrophin-1 released by cardiac fibroblasts, pointing to similar activities in vivo. Thus, hmw- and lmw-FGF-2 exert isoform-specific effects in the heart and only hmw-FGF-2 triggers cardiomyocyte hypertrophic growth. Direct effects of hmw-FGF-2 on cardiomyocytes, becoming reinforced and sustained by upregulation of cardiotrophin-1 and acting in concert with other factors, are likely to contribute to post-MI hypertrophy.
Jiang
Zhi-Sheng
ZS
Institute of Cardiovascular Disease, Nanhua University, Hengyang City, Hunan, PR China.
Jeyaraman
Madhumathy
M
Wen
Ge-Bo
GB
Fandrich
Robert R
RR
Dixon
Ian M C
IM
Cattini
Peter A
PA
Kardami
Elissavet
E
D000818:Animals; D006332:Cardiomegaly / Q000209:etiology* / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D002316:Cardiotonic Agents / Q000737:chemistry / Q000494:pharmacology; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism*; D016222:Fibroblast Growth Factor 2 / Q000737:chemistry / Q000494:pharmacology*; D008297:Male; D008970:Molecular Weight; D009203:Myocardial Infarction / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000737:chemistry / Q000494:pharmacology
D002316:Cardiotonic Agents; D016207:Cytokines; D011994:Recombinant Proteins; D016222:Fibroblast Growth Factor 2; C092073:cardiotrophin 1