Oxidant stress impairs in vivo reendothelialization capacity of endothelial progenitor cells from patients with type 2 diabetes mellitus: restoration by the peroxisome proliferator-activated receptor-gamma agonist rosiglitazone
| Autor: | Helmut Drexler, Ferdinand H. Bahlmann, Danilo Fliser, Tibor Horvath, Svenja Schulz, Hermann Haller, Nina Kirchhoff, Ulf Landmesser, Florian P. Limbourg, Sajoscha A. Sorrentino, Maja Müller, Christian Besler, Anne Limbourg, Carola Doerries |
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| Rok vydání: | 2007 |
| Předmět: |
Agonist
Male medicine.medical_specialty Endothelium medicine.drug_class Vasodilator Agents Mice Nude Blood Pressure Type 2 diabetes Nitric Oxide Models Biological Rosiglitazone Mice In vivo Reference Values Superoxides Physiology (medical) Diabetes mellitus Internal medicine medicine Animals Humans Progenitor cell Aged business.industry Stem Cells Endothelial Cells Middle Aged medicine.disease Endothelial stem cell PPAR gamma Oxidative Stress medicine.anatomical_structure Endocrinology Carotid Arteries Cholesterol Diabetes Mellitus Type 2 cardiovascular system Female Thiazolidinediones Endothelium Vascular Cardiology and Cardiovascular Medicine business Diabetic Angiopathies medicine.drug |
| Zdroj: | Circulation. 116(2) |
| ISSN: | 1524-4539 |
| Popis: | Background— Endothelial progenitor cells (EPCs) are thought to contribute to endothelial recovery after arterial injury. We therefore compared in vivo reendothelialization capacity of EPCs derived from patients with diabetes mellitus and healthy subjects. Moreover, we examined the effect of treatment with the peroxisome proliferator-activated receptor-γ agonist rosiglitazone on oxidant stress, nitric oxide (NO) bioavailability, and the in vivo reendothelialization capacity of EPCs from diabetic individuals. Methods and Results— In vivo reendothelialization capacity of EPCs from diabetic patients (n=30) and healthy subjects (n=10) was examined in a nude mouse carotid injury model. Superoxide and NO production of EPCs was determined by electron spin resonance spectroscopy. Thirty patients with diabetes mellitus were randomized to 2 weeks of rosiglitazone (4 mg BID PO) or placebo treatment. In vivo reendothelialization capacity of EPCs derived from diabetic subjects was severely reduced compared with EPCs from healthy subjects (reendothelialized area: 8±3% versus 37±10%; P phox reduced superoxide production and restored NO bioavailability and in vivo reendothelialization capacity of EPCs from diabetic patients. Importantly, rosiglitazone therapy normalized NAD(P)H oxidase activity, restored NO bioavailability, and improved in vivo reendothelialization capacity of EPCs from diabetic patients (reendothelialized area: placebo versus rosiglitazone, 8±1% versus 38±5%; P Conclusions— In vivo reendothelialization capacity of EPCs derived from individuals with diabetes mellitus is severely impaired at least partially as a result of increased NAD(P)H oxidase–dependent superoxide production and subsequently reduced NO bioavailability. Rosiglitazone therapy reduces NAD(P)H oxidase activity and improves reendothelialization capacity of EPCs from diabetic individuals, representing a potential novel mechanism whereby peroxisome proliferator-activated receptor-γ agonism promotes vascular repair. |
| Databáze: | OpenAIRE |
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