Diabetes Mellitus Enhances Vascular Matrix Metalloproteinase Activity
| Autor: | Shiro Uemura, David G. Harrison, Keun-Ho Lee, Hidetsugu Matsushita, Alexander J. Glassford, Tomoko Asagami, Philip S. Tsao, Wei Li |
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| Rok vydání: | 2001 |
| Předmět: |
Blood Glucose
Male medicine.medical_specialty Vascular smooth muscle Endothelium Physiology Gelatinase A Biology Matrix metalloproteinase medicine.disease_cause Antioxidants Muscle Smooth Vascular Streptozocin Diabetes Mellitus Experimental Rats Sprague-Dawley Mice Internal medicine medicine Animals Insulin Gelatinase RNA Messenger Enzyme Inhibitors Promoter Regions Genetic Aorta Cells Cultured Protein Kinase C Vascular tissue Macrophages Rats Endothelial stem cell Disease Models Animal Oxidative Stress Glucose Endocrinology medicine.anatomical_structure Matrix Metalloproteinase 9 Hyperglycemia Matrix Metalloproteinase 2 Cattle Endothelium Vascular Reactive Oxygen Species Cardiology and Cardiovascular Medicine Oxidative stress |
| Zdroj: | Circulation Research. 88:1291-1298 |
| ISSN: | 1524-4571 0009-7330 |
| DOI: | 10.1161/hh1201.092042 |
| Popis: | —Diabetes mellitus (DM) is a primary risk factor for cardiovascular disease. Although recent studies have demonstrated an important role for extracellular matrix metalloproteinases (MMPs) in atherosclerosis, little is known about the effects of hyperglycemia on MMP regulation in vascular cells. Gelatin zymography and Western blot analysis revealed that the activity and expression of 92-kDa (MMP-9) gelatinase, but not of 72 kDa (MMP-2) gelatinase, were significantly increased in vascular tissue and plasma of two distinct rodent models of DM. Bovine aortic endothelial cells (BAECs) grown in culture did not express MMP-9 constitutively; however, chronic (2-week) incubation with high glucose medium induced MMP-9 promoter activity, mRNA and protein expression, and gelatinase activity in BAECs. On the other hand, high glucose culture did not change MMP-9 activity from vascular smooth muscle cells or macrophages. Electron paramagnetic resonance studies indicate that BAECs chronically grown in high glucose conditions produce 70% more ROS than do control cells. Enhanced MMP-9 activity was significantly reduced by treatment with the antioxidants polyethylene glycol–superoxide dismutase andN-acetyl-l-cysteine but not by inhibitors of protein kinase C. In conclusion, vascular MMP-9 activity is increased in DM, in part because of enhanced elaboration from vascular endothelial cells, and oxidative stress plays an important role. This novel mechanism of redox-sensitive MMP-9 expression by hyperglycemia may provide a rationale for antioxidant therapy to modulate diabetic vascular complications. |
| Databáze: | OpenAIRE |
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