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Contribution of the Potassium Channels KV1.3 and KCa3.1 to Smooth Muscle Cell Proliferation in Growing Collateral Arteries
Open AccessArticle

The Lipopeptide MALP-2 Promotes Collateral Growth

Max-Planck-Institute for Heart and Lung Research, 61231 Bad Nauheim, Germany
Department of Vascular and Endovascular Surgery, University Hospital Frankfurt, 60488 Frankfurt, Germany
Cardiology and Angiology, Philipps-University Marburg, 35043 Marburg, Germany
Author to whom correspondence should be addressed.
Cells 2020, 9(4), 997;
Received: 6 April 2020 / Accepted: 14 April 2020 / Published: 16 April 2020
(This article belongs to the Special Issue Arteriogenesis and Therapeutic Neovascularization)
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. View Full-Text
Keywords: TLR2/6; femoral artery ligation; blood flow recovery; collateral growth TLR2/6; femoral artery ligation; blood flow recovery; collateral growth
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Troidl, K.; Schubert, C.; Vlacil, A.-K.; Chennupati, R.; Koch, S.; Schütt, J.; Oberoi, R.; Schaper, W.; Schmitz-Rixen, T.; Schieffer, B.; Grote, K. The Lipopeptide MALP-2 Promotes Collateral Growth. Cells 2020, 9, 997.

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