The lipopeptide MALP-2 promotes collateral growth

  • Beyond their role in pathogen recognition and the initiation of immune defense, Toll-like receptors (TLRs) are known to be involved in various vascular processes in health and disease. We investigated the potential of the lipopeptide and TLR2/6 ligand macrophage activating protein of 2-kDA (MALP-2) to promote blood flow recovery in mice. Hypercholesterolemic apolipoprotein E (Apoe)-deficient mice were subjected to microsurgical ligation of the femoral artery. MALP-2 significantly improved blood flow recovery at early time points (three and seven days), as assessed by repeated laser speckle imaging, and increased the growth of pre-existing collateral arteries in the upper hind limb, along with intimal endothelial cell proliferation in the collateral wall and pericollateral macrophage accumulation. In addition, MALP-2 increased capillary density in the lower hind limb. MALP-2 enhanced endothelial nitric oxide synthase (eNOS) phosphorylation and nitric oxide (NO) release from endothelial cells and improved the experimental vasorelaxation of mesenteric arteries ex vivo. In vitro, MALP-2 led to the up-regulated expression of major endothelial adhesion molecules as well as their leukocyte integrin receptors and consequently enhanced the endothelial adhesion of leukocytes. Using the experimental approach of femoral artery ligation (FAL), we achieved promising results with MALP-2 to promote peripheral blood flow recovery by collateral artery growth.

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Author:Kerstin TroidlORCiDGND, Christian Schubert, Ann-Kathrin Vlacil, Ramesh Chennupati, Sören Koch, Jutta Schütt, Raghav Oberoi, Wolfgang SchaperGND, Thomas Schmitz-RixenORCiDGND, Bernhard Schieffer, Karsten GroteORCiDGND
Parent Title (English):Cells
Place of publication:Basel
Document Type:Article
Date of Publication (online):2020/04/16
Date of first Publication:2020/04/16
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2020/09/22
Tag:TLR2/6; blood flow recovery; collateral growth; femoral artery ligation
Issue:(4), article 997
Page Number:14
Institutes:Medizin / Medizin
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Licence (German):License LogoCreative Commons - Namensnennung 4.0