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Arterioscler Thromb Vasc Biol. 2013 Sep;33(9):2097-104. doi: 10.1161/ATVBAHA.113.301799. Epub 2013 Jul 18.

Toll-like receptor 2/6 agonist macrophage-activating lipopeptide-2 promotes reendothelialization and inhibits neointima formation after vascular injury.

Author information

1
Department of Cardiology and Angiology, Hannover Medical School, Hannover, Germany. grote.karsten@mh-hannover.de

Erratum in

  • Arterioscler Thromb Vasc Biol. 2013 Sep;33(9). doi: 10.1161/ATVBAHA.113.301799.
  • Arterioscler Thromb Vasc Biol. 2013 Nov;33(11):e134.

Abstract

OBJECTIVE:

Reendothelialization after vascular injury (ie, balloon angioplasty or stent implantation) is clinically extremely relevant to promote vascular healing. We here investigated the therapeutic potential of the toll-like receptor 2/6 agonist macrophage-activating lipopeptide (MALP)-2 on reendothelialization and neointima formation in a murine model of vascular injury.

APPROACH AND RESULTS:

The left common carotid artery was electrically injured, and reendothelialization was quantified by Evans blue staining after 3 days. A single injection of MALP-2 (1 or 10 µg, IV) after vascular injury accelerated reendothelialization (P<0.001). Proliferation of endothelial cells at the wound margins determined by 5-ethynyl-2'-deoxyuridine incorporation was significantly higher in MALP-2-treated animals (P<0.05). Furthermore, wire injury-induced neointima formation of the left common carotid artery was completely prevented by a single injection of MALP-2 (10 µg, IV). 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 endothelial cells. MALP-2 induced a strong activation of the mitogen-activated protein kinase cascade in endothelial cells, which was attenuated in smooth muscle cells. Furthermore, MALP-2 significantly enhanced circulating monocytes and hematopoietic progenitor cells.

CONCLUSIONS:

The toll-like receptor 2/6 agonist MALP-2 promotes reendothelialization and inhibits neointima formation after experimental vascular injury via enhanced proliferation and migration of endothelial cells. Thus, MALP-2 represents a novel therapeutic option to accelerate reendothelialization after vascular injury.

KEYWORDS:

cytokines; endothelial growth factors; neointima formation; toll-like receptors; vascular system injuries

PMID:
23868938
DOI:
10.1161/ATVBAHA.113.301799
[Indexed for MEDLINE]

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