Plasminogen activator inhibitor-1 expression by brain microvessel endothelial cells is inhibited by elevated glucose
| Autor: | Anne P. Ambarian, Peter R. Kollros, Barbara A. Konkle, Paul Henrikson |
|---|---|
| Rok vydání: | 1994 |
| Předmět: |
medicine.medical_specialty
Plasmin Gene Expression Biology Blood–brain barrier Biochemistry Tissue plasminogen activator Umbilical vein Neovascularization Cellular and Molecular Neuroscience chemistry.chemical_compound Internal medicine Plasminogen Activator Inhibitor 1 medicine Animals RNA Messenger Cells Cultured Immunosorbent Techniques Urokinase Brain Blotting Northern Urokinase-Type Plasminogen Activator Endocrinology medicine.anatomical_structure Glucose chemistry Plasminogen activator inhibitor-1 Tissue Plasminogen Activator Fibroblast Growth Factor 1 Cattle Endothelium Vascular medicine.symptom Plasminogen activator medicine.drug |
| Zdroj: | Journal of neurochemistry. 63(3) |
| ISSN: | 0022-3042 |
| Popis: | Patients with diabetes are predisposed to microvascular disease. In the retina and brain, this is characterized by neovascularization and new capillary formation. Because of the potential importance of plasmin generation in these processes, we evaluated the effect of elevated glucose concentrations on expression of plasminogen activator inhibitor-1 (PAI-1), tissue plasminogen activator (tPA), and urokinase (uPA) in cultured bovine brain endothelial cells (BBEC) versus cultured bovine aortic endothelial cells (BAEC). We observed that BBEC PAI-1 mRNA levels were decreased fivefold in cells cultured in media containing 20 mM glucose compared with BBEC cultured in media with 5.5 mM glucose, whereas expression of PAI-1 mRNA in BAEC, bovine mesenteric endothelial cells, and human umbilical vein endothelial cells was not modulated under these conditions. Expression of PAI-1 protein was also inhibited by growth of BBEC in elevated glucose, but the effect was less marked than at the mRNA level. Elevated glucose did not decrease expression of PAI-1 protein by BAEC. Withdrawal of acidic fibroblast growth factor enhanced expression of PAI-1 mRNA and protein in BBEC. Expression of tPA mRNA was not affected by the glucose concentration of the medium, and uPA mRNA was not detected in our BBEC cultures. A decrease in the local tissue activity of PAI-1 by elevated glucose concentrations, with no effect on tPA or uPA expression, would lead to an increase in the plasmin activity and thereby predispose neural tissues, such as the cerebrum and retina, of diabetic patients to neovascularization. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Plný text