The anti-angiogenic factor PEDF is present in the human heart  and is regulated by anoxia in cardiac myocytes and fibroblasts.
Cardiac diseases such as myocardial infarction and heart failure are among the leading causes of death in western societies. Therapeutic angiogenesis has been suggested as a concept to combat these diseases. The biology of angiogenic factors expressed in the heart such as vascular endothelial growth factor (VEGF) is well studied, whereas data on anti-angiogenic mediators in the heart are scarce. Here we study the expression of the anti-angiogenic factor pigment epithelium-derived factor (PEDF) in the human heart and in human cardiac cells. PEDF expression could be detected in human cardiac tissue on the protein and mRNA levels. PEDF mRNA levels were significantly lower in explanted human ischemic hearts as compared to healthy hearts. Our in vitro experiments showed that human adult cardiac myocytes and fibroblasts constitutively secrete PEDF. In addition to anoxic conditions, cobalt chloride, 2,2'dipyridyl and dimethoxally glycine, which stabilize hypoxia inducible factor-alpha decreased PEDF expression. Furthermore we show that PEDF inhibits VEGF-induced sprouting. We have identified PEDF in healthy and ischemic human hearts and we show that PEDF expression is down-regulated by low oxygen levels. Therefore, we suggest a role for PEDF in the regulation of angiogenesis in the heart and propose PEDF as a possible therapeutic target in heart disease.
Rychli
Kathrin
K
Department of Internal Medicine II, Medical University Vienna, Austria.
Kaun
Christoph
C
Hohensinner
Philipp J
PJ
Dorfner
Adrian J
AJ
Pfaffenberger
Stefan
S
Niessner
Alexander
A
Bauer
Michael
M
Dietl
Wolfgang
W
Podesser
Bruno K
BK
Maurer
Gerald
G
Huber
Kurt
K
Wojta
Johann
J
D000328:Adult; D020533:Angiogenesis Inhibitors / Q000378:metabolism*; D000818:Animals; D002478:Cells, Cultured; D005136:Eye Proteins / Q000235:genetics / Q000378:metabolism*; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D000860:Hypoxia / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000166:cytology / Q000378:metabolism*; D009414:Nerve Growth Factors / Q000235:genetics / Q000378:metabolism*; D015843:Serpins / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D000099174:Pigment Epithelium-Derived Factor
D020533:Angiogenesis Inhibitors; D005136:Eye Proteins; D009414:Nerve Growth Factors; D015843:Serpins; D014157:Transcription Factors; D042461:Vascular Endothelial Growth Factor A; D000099174:Pigment Epithelium-Derived Factor