"Protective effect of Placenta Growth Factor (PIGF) against hypoxia-reoxgyenation and serum-deprivation induced apoptosis in neonatal rat cardiomyocytes"
Torry, Ronald J.
Torry, Donald S.
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SubjectApoptosis; Placenta Growth Factor (PIGF); Hypoxia; Angiogenesis; Vascular Endothelial Growth Factor (VEGF); Ischemic heart disease
Placenta growth factor (PlGF) is known to induce angiogenesis and protect placental trophoblast from apoptosis. We have shown that PlGF mRNA expression is increased in hypoxic human myocardium and in rat neonatal cardiomyocytes. However, little is known regarding the function of PlGF in heart tissue. Others have shown that PlGF or PlGF/VEGF significantly inhibited apoptosis in endothelial cells from PlGF knockout mice and we have shown that PlGF rescues cultured trophoblast from apoptosis induced by serum deprivation. Accordingly, our hypothesis is that PlGF protects cardiomyocytes from ischemia-induced or serum deprivation-induced apoptosis. The role of PlGF will be investigated during cardiomyocyte apoptosis induced by serum-deprivation and hypoxia-reoxygenation (H/R)--physiological conditions relevant to ischemic cardiomyopathy. Hypoxic conditions were established by culturing the cells at 1-2% O2. Caspase-3,7 luminescence assay (Promega) was used to determine the level of activated Caspases 3 and 7. The caspase family of cysteine proteases, especially caspase-3, is central in amplifying the cascade of proteolysis that culminates in cell death. Serum-deprivation and H/R have been found to be consistent methods of creating ischemic stresses and inducing apoptosis in rat cardiomyocytes. Serum-deprivation produced a 1.55 fold increase of apoptosis over normoxic values (n=10). H/R lead to a 1.98 fold increase of apoptosis (n=1). Our preliminary data suggest that a PlGF (25ng/ml) or PlGF/VEGF (25ng/ml each) does not reduce apoptosis induced by serum-deprivation. However, an 8 hour pretreatment of PlGF (25ng/ml) by itself reduced caspase 3 activity by 25.5% (n=1) and 30.7% (n=3) during hypoxia or serum deprivation, respectively. The preliminary data show an 8 hour pretreatment with PlGF/VEGF (25ng/ml each) decreased caspase activity more than PlGF (25ng/ml) alone. Thus, early evidence indicates that pretreatment with PlGF or PlGF/VEGF may protect cardiomyocytes from hypoxia-reoxygenation and/or serum deprivation-induced apoptosis.
Kyle Bohman, Marin Schweizer and Bob Berendt are all Drake University students. Ronald J. Torry is Associate Professor of Pharmacology at Drake University. Donald S. Torry is a faculty member at the Southern Illinois University School of Medicine.
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