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The anti-angiogenic factor PEDF is present in the human heart and is regulated by anoxia in cardiac myocytes and fibroblasts.
J Cell Mol Med ; 14(1-2): 198-205, 2010 Jan.
Article en En | MEDLINE | ID: mdl-19298519
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Serpinas / Inhibidores de la Angiogénesis / Miocitos Cardíacos / Proteínas del Ojo / Fibroblastos / Hipoxia / Factores de Crecimiento Nervioso Tipo de estudio: Prognostic_studies Límite: Adult / Animals / Humans Idioma: En Revista: J Cell Mol Med Asunto de la revista: BIOLOGIA MOLECULAR Año: 2010 Tipo del documento: Article País de afiliación: Austria Pais de publicación: Reino Unido

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Serpinas / Inhibidores de la Angiogénesis / Miocitos Cardíacos / Proteínas del Ojo / Fibroblastos / Hipoxia / Factores de Crecimiento Nervioso Tipo de estudio: Prognostic_studies Límite: Adult / Animals / Humans Idioma: En Revista: J Cell Mol Med Asunto de la revista: BIOLOGIA MOLECULAR Año: 2010 Tipo del documento: Article País de afiliación: Austria Pais de publicación: Reino Unido