Hypoxia increases placenta growth factor expression in human myocardium and cultured neonatal rat cardiomyocytes.

Abstract

BACKGROUND:

Placenta growth factor (PlGF) 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 PlGF expression in heart tissue.

METHODS:

We determined expression changes in PlGF 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 PlGF 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 PlGF mRNA than biopsies from allografts without fibrin (n = 11; p < 0.05). PlGF 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 cardiomyocytes constitutively expressed PlGF/VEGFR1 under normoxia. PlGF expression was increased 3.88 +/- 0.62-fold after 12 hours (n = 6; p </= 0.05) and 3.64 +/- 0.41-fold after 24 hours of hypoxia (n = 6; p <or= 0.05). Shorter periods of hypoxia, conditioned media from hypoxic cells and cyclical stretch did not significantly alter PlGF 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 PlGF may facilitate cardiac healing after myocardial hypoxia/ischemia.

• Authors: Ronald J Torry, Robert J Tomanek, Wei Zheng, Steven J Miller, Carlos A Labarrere, Donald S Torry
• Journal: The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation (J Heart Lung Transplant) Vol. 28 Issue 2 Pg. 183-90 (Feb 2009) ISSN: 1557-3117 [Electronic] United States
• PMID: 19201345 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• DNA Primers
• PGF protein, human
• Pgf protein, rat
• Pregnancy Proteins
• RNA, Messenger
• Placenta Growth Factor
• Vascular Endothelial Growth Factor Receptor-1

Topics

• Animals
• Animals, Newborn
• Biopsy
• Cell Hypoxia (physiology)
• Cells, Cultured
• DNA Primers
• Heart (physiology)
• Heart Transplantation (pathology, physiology)
• Humans
• Hypoxia (physiopathology)
• Myocytes, Cardiac (cytology, physiology)
• Neovascularization, Pathologic (physiopathology)
• Placenta Growth Factor
• Pregnancy Proteins (genetics)
• RNA, Messenger (genetics)
• Rats
• Reverse Transcriptase Polymerase Chain Reaction
• Tissue Donors
• Transplantation, Homologous
• Vascular Endothelial Growth Factor Receptor-1 (genetics)