title: Adrenomedullin induces lymphangiogenesis and ameliorates secondary lymphoedema.
abstract: OBJECTIVE
  Adrenomedullin (AM) is a multifunctional peptide hormone that plays a significant role in vasodilation and angiogenesis. Lymphoedema is a common but refractory disorder that is difficult to be treated with conventional therapy. We therefore investigated whether AM promotes lymphangiogenesis and improves lymphoedema.
  
  
  RESULTS
  The effects of AM on lymphatic endothelial cells (LEC) were investigated. AM promoted proliferation, migration, and network formation of cultured human lymphatic microvascular endothelial cells (HLMVEC). AM increased intracellular cyclic adenosine monophosphate (cAMP) level in HLMVEC. The cell proliferation induced by AM was inhibited by a cAMP antagonist and mitogen-activated protein kinase kinase (MEK) inhibitors. Phosphorylated extracellular signal-regulated kinase (ERK) in HLMVEC was increased by AM. Continuous administration of AM (0.05 microg/kg/min) to BALB/c mice with tail lymphoedema resulted in a decrease in lymphoedema thickness. AM treatment increased the number of lymphatic vessels and blood vessels in the injury site.
  
  
  CONCLUSIONS
  AM promoted LEC proliferation at least in part through the cAMP/MEK/ERK pathway, and infusion of AM induced lymphangiogenesis and improved lymphoedema in mice.
authors: Department of Regenerative Medicine and Tissue Engineering, National Cardiovascular Center Research Institute, 5-7-1 Fujishirodai, Suita, Osaka 565-8565, Japan.
authors: Donghao
authors: D
authors: Jin
authors: Kazuhiko
authors: K
authors: Harada
authors: Shunsuke
authors: S
authors: Ohnishi
authors: Kenich
authors: K
authors: Yamahara
authors: Kenji
authors: K
authors: Kangawa
authors: Noritoshi
authors: N
authors: Nagaya
mesh_terms: D053607:Adrenomedullin / Q000502:physiology*; D000818:Animals; D002465:Cell Movement; D049109:Cell Proliferation; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000502:physiology; D004195:Disease Models, Animal; D004729:Endothelium, Lymphatic / Q000166:cytology / Q000502:physiology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000502:physiology; D006801:Humans; D042583:Lymphangiogenesis / Q000502:physiology*; D008209:Lymphedema / Q000188:drug therapy / Q000503:physiopathology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D020929:Mitogen-Activated Protein Kinase Kinases / Q000502:physiology; D018919:Neovascularization, Physiologic / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology; D014664:Vasodilation / Q000502:physiology
chemical_list: D053607:Adrenomedullin; D000242:Cyclic AMP; D048049:Extracellular Signal-Regulated MAP Kinases; D020929:Mitogen-Activated Protein Kinase Kinases