Fibroblast growth factor 2 isoforms and cardiac hypertrophy.
Fibroblast growth factor 2 (FGF-2), a multifunctional polypeptide that affects cell growth and differentiation and becomes upregulated by stress, is expressed as AUG-initiated 18 kDa FGF-2 or CUG-initiated 21-34 kDa (hi-FGF-2) isoforms. Animal models have provided strong evidence that FGF-2 is essential for the manifestation of overload- and angiotensin-induced cardiac hypertrophy. Nevertheless, studies to-date have not discriminated between the activities of 18 kDa FGF-2 and hi-FGF-2. Our recent work has pointed to a potent pro-hypertrophic effect of added hi-FGF-2, and a pro-apoptotic effect of sustained intracrine hi-FGF-2 signaling. In the future, it will be important to differentiate between the activities of the different FGF-2 isoforms in the context of adaptive and maladaptive myocardial hypertrophy and heart failure. Based on all available evidence, we propose that while the 18-kDa FGF-2 is a component of an adaptive trophic response, a switch to hi-FGF-2 accumulation would exacerbate hypertrophy and contribute to cell death, thus driving the myocardium towards a maladaptive phenotype.
Institute of Cardiovascular Sciences 3008, St. Boniface Research Centre and Departments of Human Anatomy and Cell Sciences and Physiology, 351 Tache Ave., University of Manitoba, Winnipeg, Manitoba, Canada R2H 2A6. ekardami@sbrc.ca
Elissavet
E
Kardami
Zhi-Sheng
ZS
Jiang
Sarah K
SK
Jimenez
Cheryl J
CJ
Hirst
Farah
F
Sheikh
Peter
P
Zahradka
Peter A
PA
Cattini
D000804:Angiotensin II / Q000378:metabolism; D000818:Animals; D006332:Cardiomegaly / Q000378:metabolism*; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism*; D006801:Humans; D009206:Myocardium / Q000378:metabolism*; D020033:Protein Isoforms / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*
D020033:Protein Isoforms; D016222:Fibroblast Growth Factor 2; D000804:Angiotensin II