Hypoxia Increases Placenta Growth Factor Expression in Human Myocardium and Cultured Neonatal Rat Cardiomyocytes

Ronald J. Torry, Robert J. Tomanek, Wei Zheng, Steven Miller, Carlos A. Labarrere, Donald S. Torry

Research output: Contribution to journalArticle

32 Citations (Scopus)

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 ≤ 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.

Original languageEnglish
Pages (from-to)183-190
Number of pages8
JournalJournal of Heart and Lung Transplantation
Volume28
Issue number2
DOIs
StatePublished - Feb 2009

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Cardiac Myocytes
Myocardium
Fibrin
Allografts
Biopsy
Messenger RNA
Hypoxia
Placenta Growth Factor
Pathologic Neovascularization
Troponin I
Growth Factor Receptors
Conditioned Culture Medium
Microvessels
Myocardial Ischemia
Extracellular Matrix
Coronary Artery Disease
Biomarkers
Tissue Donors
Serum

ASJC Scopus subject areas

  • Transplantation
  • Cardiology and Cardiovascular Medicine
  • Pulmonary and Respiratory Medicine
  • Surgery

Cite this

Hypoxia Increases Placenta Growth Factor Expression in Human Myocardium and Cultured Neonatal Rat Cardiomyocytes. / Torry, Ronald J.; Tomanek, Robert J.; Zheng, Wei; Miller, Steven; Labarrere, Carlos A.; Torry, Donald S.

In: Journal of Heart and Lung Transplantation, Vol. 28, No. 2, 02.2009, p. 183-190.

Research output: Contribution to journalArticle

Torry, Ronald J. ; Tomanek, Robert J. ; Zheng, Wei ; Miller, Steven ; Labarrere, Carlos A. ; Torry, Donald S. / Hypoxia Increases Placenta Growth Factor Expression in Human Myocardium and Cultured Neonatal Rat Cardiomyocytes. In: Journal of Heart and Lung Transplantation. 2009 ; Vol. 28, No. 2. pp. 183-190.
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AU - Torry, Donald S.

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