Brain derived neurotrophic factor is an endothelial cell survival factor required for intramyocardial vessel stabilization
| Autor: | Rebecca T. Hahn, C.F. Ibanez, Barbara L. Hempstead, Rosemary Kraemer, Shiyang Wang, Michelle I. Lin, Michael J. Donovan, Thomas Ringstedt, Shahin Rafii, Phi Wiegn |
|---|---|
| Rok vydání: | 2000 |
| Předmět: |
Heart Defects
Congenital Endothelium Cell Survival Angiogenesis medicine.medical_treatment Apoptosis Cell Communication Receptor tyrosine kinase Mice Coronary Circulation medicine Animals Receptor trkB Molecular Biology Crosses Genetic Mice Knockout Brain-derived neurotrophic factor biology Reverse Transcriptase Polymerase Chain Reaction Brain-Derived Neurotrophic Factor Growth factor Heart Anatomy Coronary Vessels Capillaries Cell biology Mice Inbred C57BL Vascular endothelial growth factor B Endothelial stem cell medicine.anatomical_structure Animals Newborn nervous system biology.protein Endothelium Vascular Developmental Biology Neurotrophin |
| Zdroj: | Development. 127:4531-4540 |
| ISSN: | 1477-9129 0950-1991 |
| DOI: | 10.1242/dev.127.21.4531 |
| Popis: | Brain derived neurotrophic factor, BDNF, is a neurotrophin best characterized for its survival and differentiative effects on neurons expressing the trk B receptor tyrosine kinase. Although many of these neurons are lost in the BDNF−/− mouse, the early postnatal lethality of these animals suggests a wider function for this growth factor. Here, we demonstrate that deficient expression of BDNF impairs the survival of endothelial cells in intramyocardial arteries and capillaries in the early postnatal period, although the embryonic vasculature can remodel into arteries, capillaries and veins. BDNF deficiency results in a reduction in endothelial cell-cell contacts and in endothelial cell apoptosis, leading to intraventricular wall hemorrhage, depressed cardiac contractility and early postnatal death. Vascular hemorrhage is restricted to cardiac vessels, reflecting the localized expression of BDNF and trk B by capillaries and arterioles in this vascular bed. Conversely, ectopic BDNF overexpression in midgestational mouse hearts results in an increase in capillary density. Moreover, BDNF activation of endogenous trk B receptors supports the survival of cardiac microvascular endothelial cells cultured from neonatal mice. These results establish an essential role for BDNF in maintaining vessel stability in the heart through direct angiogenic actions on endothelial cells. |
| Databáze: | OpenAIRE |
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