Impairment in Ischemia-Induced Neovascularization in Diabetes
| Autor: | Gérard Tobelem, Jean-Sébastien Silvestre, Bernard I. Levy, Laurence Lecomte-Raclet, Micheline Duriez, Sophie Le Ricousse-Roussanne, Radia Tamarat, Michel Clergue, Véronique Barateau |
|---|---|
| Rok vydání: | 2004 |
| Předmět: |
medicine.medical_specialty
business.industry medicine.medical_treatment Ischemia Streptozotocin Revascularization medicine.disease Pathology and Forensic Medicine Transplantation Neovascularization medicine.anatomical_structure Endocrinology Diabetes mellitus Internal medicine medicine Bone marrow Progenitor cell medicine.symptom business medicine.drug |
| Zdroj: | The American Journal of Pathology. 164:457-466 |
| ISSN: | 0002-9440 |
| DOI: | 10.1016/s0002-9440(10)63136-7 |
| Popis: | Mechanisms that hinder ischemia-induced neovascularization in diabetes remain poorly understood. We hypothesized that endogenous bone marrow mononuclear cell (BM-MNC) dysfunction may contribute to the abrogated postischemic revascularization reaction associated with diabetes. We first analyzed the effect of diabetes (streptozotocin, 40 mg/kg) on BM-MNC pro-angiogenic potential in a model of surgically induced hindlimb ischemia. In nondiabetic animals, transplantation of BM-MNCs isolated from nondiabetic animals raised the ischemic/nonischemic angiographic score, capillary number, and blood flow recovery by 1.8-, 2.7-, and 2.2-fold, respectively, over that of PBS-injected nondiabetic animals (P < 0.05). Administration of diabetic BM-MNCs also improved the neovascularization reaction in ischemic hindlimbs of nondiabetic mice but to a lesser extent from that observed with nondiabetic BM-MNC transplantation. In diabetic mice, injection of nondiabetic BM-MNCs was still more efficient than that of diabetic BM-MNCs. Such BM-MNC dysfunction was associated with the impairment of diabetic BM-MNC capacity to differentiate into endothelial progenitor cells (EPCs) in vitro and to participate in vascular-like structure formation in a subcutaneous Matrigel plug. Placenta growth factor (PlGF) administration improved by sixfold the number of EPCs differentiated from diabetic BM-MNCs in vitro and enhanced ischemic/nonischemic angiographic score, capillary number and blood flow recovery by 1.9-, 1.5- and 1.6-fold, respectively, over that of untreated diabetic animals (P < 0.01). Endogenous BM-MNC pro-angiogenic potential was affected in diabetes. Therapeutic strategy based on PlGF administration restored such defects and improved postischemic neovascularization in diabetic mice. |
| Databáze: | OpenAIRE |
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