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Negative inotropic effect of basic fibroblast growth factor on adult rat cardiac myocyte
Y Ishibashi1, Y Urabe, H Tsutsui
1Research Institute of Angiocardiology and Cardiovascular Clinic, Kyushu University School of Medicine, Fukuoka, Japan.
Insights
Basic fibroblast growth factor (bFGF) negatively impacts heart muscle contraction. This finding in cardiac myocytes suggests bFGF may contribute to dysfunction in conditions like ischemia-reperfusion and transplant rejection.
Area of Science:
- Cardiology
- Molecular Biology
- Cell Physiology
Background:
- Basic fibroblast growth factor (bFGF) is elevated in myocardial conditions like ischemia-reperfusion and allograft rejection.
- The functional impact of bFGF on myocardial contractility remains largely uncharacterized.
Purpose of the Study:
- To investigate the direct effects of bFGF on the contractility of adult cardiac myocytes.
- To elucidate the underlying mechanisms of bFGF-mediated effects on myocardial function.
Main Methods:
- Isolated adult rat cardiac myocytes were utilized to assess contractility.
- Dose- and time-dependent effects of bFGF were evaluated.
- Neutralizing antibodies and other growth factors were used to confirm specificity.
Main Results:
- bFGF demonstrated a direct, concentration- and time-dependent negative inotropic effect on cardiac myocytes.
- This effect was specific to bFGF, as other growth factors did not elicit similar responses.
- bFGF significantly reduced peak intracellular calcium transients, suggesting altered calcium handling.
Conclusions:
- Despite its role as a growth promoter, bFGF exhibits acute negative inotropic effects on adult cardiac myocytes.
- These effects are likely mediated by alterations in intracellular calcium homeostasis.
- The negative inotropic action of bFGF may contribute to cardiac dysfunction observed in ischemia-reperfusion injury and heart transplant rejection.
Background:
Basic fibroblast growth factor (bFGF) is highly expressed in the myocardium in some cardiac disorders, such as ischemia-reperfusion and cardiac allograft rejection. However, whether bFGF has any effects on myocardial contraction is unknown.
Methods And Results:
We examined the effects of bFGF on myocardial contractility using isolated adult rat cardiac myocyte preparations. bFGF exerted a direct negative inotropic effect that was concentration and time dependent. The pretreatment of myocytes with a neutralizing anti-bFGF antibody (100 ng/mL) abolished the negative inotropic effects of bFGF (100 ng/mL). Platelet-derived growth factor (12.5 ng/mL) and transforming growth factor-beta (1 ng/mL) did not exert such effects, which indicated that bFGF-induced negative inotropism was considered to be specific for this growth factor. bFGF decreased the peak intracellular Ca2+ transient by 46% during systole. The enhanced production of nitric oxide was unlikely to be responsible for the bFGF-induced negative inotropic effect.
Conclusions:
bFGF, primarily a potent growth promoter, produced acute negative inotropic effects in the adult cardiac myocyte that could have resulted from alterations in intracellular Ca2+ homeostasis. The negative inotropic effect of bFGF may contribute to myocardial dysfunction associated with ischemia-reperfusion injury and heart transplant rejection.