TY - JOUR A1 - Troidl, Kerstin A1 - Schubert, Christian A1 - Vlacil, Ann-Kathrin A1 - Chennupati, Ramesh A1 - Koch, Sören A1 - Schütt, Jutta A1 - Oberoi, Raghav A1 - Schaper, Wolfgang A1 - Schmitz-Rixen, Thomas A1 - Schieffer, Bernhard A1 - Grote, Karsten T1 - The lipopeptide MALP-2 promotes collateral growth T2 - Cells N2 - 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. KW - TLR2/6 KW - femoral artery ligation KW - blood flow recovery KW - collateral growth Y1 - 2020 UR - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/55575 UR - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-555759 SN - 2073-4409 VL - 9 IS - (4), article 997 PB - MDPI CY - Basel ER -