Journal
JOURNAL OF HEART AND LUNG TRANSPLANTATION
Volume 28, Issue 2, Pages 183-190Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.healun.2008.11.917
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Funding
- NHLBI NIH HHS [R01-HL075446, R01 HL075446, R15 HL072802, R15-HL72802-01] Funding Source: Medline
- NICHD NIH HHS [R01-HD36830, R01 HD036830, R01 HD036830-08] Funding Source: Medline
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Background: Placenta growth factor (PIGF) plays an important role in pathologic angiogenesis and is believed to be an independent biomarker in patients with coronary artery disease. However, little is known regarding the regulation of PIGF expression in heart tissue. Methods: We determined expression changes in PIGF and its receptor, VEGFR1, in normal and abnormal biopsies from human cardiac allografts and in cardiomyocytes cultured under hypoxia or cyclical stretch conditions. Results: Human donor myocardium and biopsies from allografts without fibrin deposits expressed PIGF and VEGFR1 mRNA. Biopsies (n = 7) with myocardial fibrin, elevated serum cardiac troponin I titers (P < 0.03) and cellular infiltrates (p < 0.05) expressed 1.6-fold more PIGF mRNA than biopsies from allografts without fibrin (n 11; P < 0.05). PIGF protein was localized in cardiomyocytes, extracellular matrix and some microvessels in areas with fibrin deposition. VEGFR1 mRNA expression was not different between groups. Cultured neonatal rat cardioinyocytes constitutively expressed PIGF/VEGFR1 under normoxia. PIGF expression was increased 3.88 +/- 0.62-fold after 12 hours (n = 6; p 75 0.05) and 3.64 +/- 0.41-fold after 24 hours of hypoxia (n = 6; p <= 0.05). Shorter periods of hypoxia, conditioned media from hypoxic cells and cyclical stretch did not significantly alter PIGF or VEGFR1 expression. Conclusions: Cardiomyocyte PIGF expression is upregulated by hypoxia in vitro and its expression increases significantly in allografts with myocardial damage. Collectively, these results provide important temporal and spatial evidence that endogenous PIGF may facilitate cardiac healing after myocardial hypoxia/ischemia. J Heart Lung Transplant 2009;28:183-90. Copyright (C) 2009 by the International Society for Heart and Lung Trans plantation.
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