Arteriogenesis requires toll-like receptor 2 and 4 expression in bone-marrow derived cells
| Autor: | Daphne de Groot, Leo Timmers, Imo E. Hoefer, Jan J. Piek, J. Karlijn van Keulen, Gerard Pasterkamp, Dominique P.V. de Kleijn, Rene T. Haverslag, Pieter T. Bot, Sebastian Grundmann, A.H. Schoneveld |
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| Přispěvatelé: | Amsterdam Cardiovascular Sciences, Cardiology |
| Rok vydání: | 2010 |
| Předmět: |
Lipopolysaccharide
Neovascularization Physiologic Bone Marrow Cells Biology chemistry.chemical_compound Mice Downregulation and upregulation medicine Animals Receptor Molecular Biology Bone Marrow Transplantation Toll-like receptor Reverse Transcriptase Polymerase Chain Reaction Arteries Flow Cytometry Immunity Innate Mice Mutant Strains Toll-Like Receptor 2 Transplantation Toll-Like Receptor 4 medicine.anatomical_structure chemistry Immunology Tumor necrosis factor alpha Arteriogenesis Bone marrow Cardiology and Cardiovascular Medicine |
| Zdroj: | Journal of molecular and cellular cardiology, 50(1), 25-32. Academic Press Inc. |
| ISSN: | 1095-8584 0022-2828 |
| Popis: | Adaptive collateral growth (arteriogenesis) is an important protective mechanism against ischemic injury in patients with cardiovascular disease. Arteriogenesis involves enlargement of pre-existent arterial anastomoses and shares many mechanistic similarities with inflammatory processes. Although infusion of the Toll-like receptor (TLR) 4 ligand lipopolysaccharide (LPS) has shown to result in a significant stimulation of arteriogenesis and both Toll-like receptor 2 and 4 are involved in structural arterial adaptations, the requirement for TLRs in arteriogenesis has not yet been established. We therefore subjected TLR 2 null and TLR 4 defective mice to unilateral femoral artery occlusion. At 7 days, both TLR 2 null and TLR 4 defective mice showed a significant reduction (similar to 35%) of collateral perfusion. Histological staining showed that TLR 2 and TLR 4 expression during arteriogenesis is mostly restricted to infiltrating leukocytes. To distinguish between the functional importance of vascular and leukocytic TLRs in arteriogenesis, cross-over bone marrow transplantation was performed 6 weeks before femoral artery occlusion. Perfusion measurements showed that transplantation of wild-type bone marrow into TLR 2 null and TLR 4 defective mice rescued the impaired arteriogenesis, while injection of TLR 2 null and TLR 4 defective bone marrow into wild-type mice significantly reduced collateral vessel growth to levels of TLR null/defective mice. RT-PCR analysis demonstrated a significant upregulation of two endogenous TLR ligands EDA and Hsp60 (91.7 fold and 1.9 fold respectively) in regions of collateral vessel formation. This study illustrates the involvement of TLR 2 and TLR 4 in adaptive collateral artery growth and shows the importance of TLR 2 and 4 expression by bone-marrow derived cells for this process. (C) 2010 Elsevier Ltd. All rights reserved |
| Databáze: | OpenAIRE |
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