Abstract 11704: The Toll-Like Receptor 2/6 Agonist MALP-2 Promotes Reendothelialization Following Vascular Injury
Background: Interventional balloon angioplasty induces a massive vascular injury. In this regard, insufficient or decelerated reendothelialization impairs vascular healing and contributes to maladaptive processes in terms of neointimal proliferation. Recently, we identified pro-endothelial properties of the Toll-like receptor (TLR) 2/6 agonist MALP-2. Therefore, we now investigated a potential therapeutic application of MALP-2 to improve reendothelialization in a murine model of experimental vascular injury.
Methods and Results: The left Arteria carotis communis of C57BL/6 mice was exposed to an electric pulse (2 W, 2 s) over a length of 4 mm by an electrode. The induced endothelial damage was quantified after 3 d in the en face prepared Arteria carotis by Evans Blue staining. A single injection of MALP-2 (1 and 10 µg, i.v.) directly after vascular injury dose-dependently promoted reendothelialization (23% and 28%, n=12-18, p<0.001) which could be blocked by previous administration of neutralizing antibodies targeted against TLR2 and TLR6. Of note, no neointima formation in response to MALP-2 was observed in this model. In vitro, MALP-2 induced proliferation (BrdU-incorporation) and closure of an artificial wound (scratch assay) of isolated primary endothelial cells but not of isolated primary smooth muscle cells (n=4-5, p<0.05). Protein array and ELISA analysis of ex vivo stimulated carotid segments and isolated primary cells revealed the release of chemokines such as the growth factors G-CSF and GM-CSF especially from the uninjured vascular area and mainly from endothelial cells.
Conclusion: MALP-2 promotes in vivo reendothelialization following experimental vascular injury. The underlying mechanism for this regenerative process implies augmented release of growth factors from the intact endothelium and enhanced proliferation and migration of endothelial cells. Thus, the TLR2/6 agonist MALP-2 may represent a therapeutic option to improve reendothelialization following vascular injury.
- Interventional cardiology
- Growth factors
- Smooth muscle
- Transcatheter Aortic Valve Implantation
- © 2011 by American Heart Association, Inc.