Diabetologia, 2004-06, Vol.47 (6), p.1055-1063
2004
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- Autor(en) / Beteiligte
- Titel
- Nerve growth factor supplementation reverses the impairment, induced by Type 1 diabetes, of hindlimb post-ischaemic recovery in mice
- Ist Teil von
- Diabetologia, 2004-06, Vol.47 (6), p.1055-1063
- Ort / Verlag
- Berlin: Springer
- Erscheinungsjahr
- 2004
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- Type 1 diabetes increases the risk of peripheral ischaemia and impairs recovery once ischaemia occurs, probably because the healing process is hampered by diabetes-induced endothelial dysfunction. In normoglycaemic mice subjected to limb ischaemia, blockade of nerve growth factor (NGF) compromises reparative angiogenesis. In the present study, we evaluated if expressional alterations of endogenous NGF system components are associated with diabetes-related impairment in neovascularisation. In addition, we tested whether the correction of NGF liabilities benefits post-ischaemic healing of Type 1 diabetic animals. Unilateral hindlimb ischaemia was produced in streptozotocin-induced Type 1 diabetic mice. Purified murine NGF (20 microg daily for 14 days) or PBS were injected into ischaemic adductors. Non-diabetic mice given PBS served as controls. Hindlimb blood flow was analysed sequentially for up to 14 days. At necroscopy, adductors were removed for quantification of microvessel density, endothelial cell apoptosis and NGF receptor expression. NGF content was determined by ELISA three days after ischaemia. In vitro, we tested whether NGF protects endothelial cells from apoptosis induced by high glucose and whether vascular endothelial growth factor-A (VEGF-A) is involved in this beneficial effect. Muscles removed from Type 1 diabetic mice showed reduced NGF content and up-regulation of the NGF p75 receptor. NGF supplementation promoted capillarisation and arteriogenesis, reduced apoptosis, and accelerated blood flow recovery. NGF stimulated VEGF-A production by human endothelial cells incubated in high-glucose medium and conferred resistance against high-glucose-induced apoptosis via a VEGF-A-mediated mechanism. NGF protects endothelial cells from apoptosis induced by Type 1 diabetes and facilitates reparative neovascularisation. The findings may open up new therapeutic options for the treatment of diabetic complications.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0012-186XeISSN: 1432-0428DOI: 10.1007/s00125-004-1424-5Titel-ID: cdi_proquest_miscellaneous_66661113
- Format
- –
- Schlagworte
- Animals, Apoptosis - drug effects, Apoptosis - physiology, Biological and medical sciences, Capillaries - drug effects, Capillaries - pathology, Capillaries - physiopathology, Cell Survival, Diabetes Mellitus, Experimental - complications, Diabetes Mellitus, Experimental - drug therapy, Diabetes Mellitus, Experimental - physiopathology, Diabetes Mellitus, Type 1 - complications, Diabetes Mellitus, Type 1 - drug therapy, Diabetes Mellitus, Type 1 - physiopathology, Diabetes. Impaired glucose tolerance, Drug Administration Schedule, Drug Evaluation, Preclinical - methods, Endocrine pancreas. Apud cells (diseases), Endocrinopathies, Endothelium, Vascular - injuries, Endothelium, Vascular - pathology, Endothelium, Vascular - physiopathology, Fundamental and applied biological sciences. Psychology, Gene Expression, Hindlimb - blood supply, Hindlimb - drug effects, Hindlimb - injuries, Ischemia - complications, Ischemia - drug therapy, Ischemia - physiopathology, Male, Medical sciences, Mice, Muscle, Skeletal - drug effects, Muscle, Skeletal - physiopathology, Muscle, Skeletal - ultrastructure, Neovascularization, Pathologic - genetics, Neovascularization, Pathologic - physiopathology, Neovascularization, Physiologic - drug effects, Neovascularization, Physiologic - physiology, Nerve Growth Factor - antagonists & inhibitors, Nerve Growth Factor - genetics, Nerve Growth Factor - therapeutic use, Receptor, Nerve Growth Factor, Receptors, Nerve Growth Factor - antagonists & inhibitors, Receptors, Nerve Growth Factor - drug effects, Receptors, Nerve Growth Factor - genetics, Reperfusion, Retinal Vessels - physiology, Retinal Vessels - ultrastructure, Striated muscle. Tendons, Umbilical Veins - cytology, Umbilical Veins - drug effects, Umbilical Veins - physiology, Vascular Endothelial Growth Factor A - metabolism, Vertebrates: osteoarticular system, musculoskeletal system