The lipopeptide MALP-2 promotes collateral growth
| Autor: | Wolfgang Schaper, Ramesh Chennupati, Bernhard Schieffer, Sören Koch, Ann-Kathrin Vlacil, Karsten Grote, Kerstin Troidl, Raghav Oberoi, Jutta Schütt, Thomas Schmitz-Rixen, Christian Schubert |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Male
0301 basic medicine Femoral artery 030204 cardiovascular system & hematology Pharmacology TLR2/6 Monocytes Mice chemistry.chemical_compound 0302 clinical medicine Phosphorylation Receptor lcsh:QH301-705.5 Mesenteric arteries Mice Inbred BALB C collateral growth Cell adhesion molecule General Medicine Immunohistochemistry Femoral Artery Vasodilation Endothelial stem cell medicine.anatomical_structure Blood Circulation Artery Neovascularization Physiologic Nitric Oxide Article Nitric oxide Lipopeptides 03 medical and health sciences Apolipoproteins E medicine.artery medicine Animals ddc:610 Cell Proliferation blood flow recovery Macrophages Endothelial Cells femoral artery ligation Toll-Like Receptor 2 Capillaries Mice Inbred C57BL Laser Speckle Contrast Imaging Toll-Like Receptor 6 030104 developmental biology lcsh:Biology (General) chemistry Nitric Oxide Synthase Ex vivo |
| Zdroj: | Cells Volume 9 Issue 4 Cells, Vol 9, Iss 997, p 997 (2020) |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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