Abstract 14223: The Toll-Like Receptor 2/6 Agonist MALP-2 Promotes Reendothelialization Following Vascular Injury
Background: Reendothelialization following vascular injury after balloon angioplasty or stent implantation is clinically extremely relevant to promote vascular healing and prevent fatal events such as stent thrombosis and restenosis. We already identified the importance of Toll-like receptor (TLR) 2/6 for endothelial regeneration. We now investigated the therapeutic potential of the TLR2/6 agonist MALP-2 on reendothelialization in a murine model of vascular injury.
Methods and Results: The left common carotid artery of C57BL/6N mice was experimentally injured and reendothelialization was quantified by Evans Blue staining after 3 days in en face prepared vessels. A single intravenous injection of MALP-2 (1 or 10 µg) following vascular injury dose-dependently accelerated reendothelialization up to 3.5-fold (n=12-18, P<0.001) which was abolished by administration of neutralizing antibodies against TLR2 and TLR6. Proliferation of endothelial cells at the wound margins determined by EdU-incorporation was significantly higher in MALP-2 treated animals (P<0.05). In vitro, MALP-2 induced proliferation (BrdU-incorporation) and closure of an artificial wound of endothelial cells (P<0.05) but not of smooth muscle cells. Protein array and ELISA analysis of isolated primary endothelial cells and ex vivo stimulated carotid segments revealed that MALP-2 stimulated the release of multiple growth factors and cytokines predominantly from intact endothelium of the not injured carotid artery.
Conclusions: Administration of the TLR2/6 agonist MALP-2 promotes reendothelialization following experimental vascular injury via augmented release of growth factors and cytokines from the endothelium and enhanced proliferation and migration of endothelial cells. Thus, MALP-2 represents a novel therapeutic option to accelerate reendothelialization following vascular injury.
- © 2012 by American Heart Association, Inc.