title: Leptin promotes the mobilization of vascular progenitor cells and neovascularization by NOX2-mediated activation of MMP9.
abstract: OBJECTIVE
  Bone marrow (BM) progenitors participate in new vessel formation and endothelial repair. The leptin receptor (ObR) is expressed on hematopoietic cells; however, the effects of leptin on BM progenitor cells and their angiogenic potential are unknown.
  
  
  RESULTS
  In the present study, we show that the short-term administration of leptin (over five consecutive days) into wild-type mice increased the number of circulating, BM-derived sca-1(+), flk-1(+) vascular progenitors, 95 ± 1.7% of which also expressed ObR. Ex vivo stimulation of BM cells with leptin enhanced the expression of NADPH oxidase isoform 2 (NOX2), and the leptin-induced increase in reactive oxygen species production, matrix metalloproteinase-9 (MMP9) expression and circulating soluble KitL levels was absent in mice lacking NOX2. Furthermore, intraperitoneal injections of leptin improved perfusion and increased the number of BM-derived, CD31-positive endothelial cells in ischaemic hindlimbs after femoral artery ligation. The effects of leptin on the mobilization of sca-1(+), flk-1(+) cells and neovascularization were abolished in mice transplanted with BM from ObR-deficient and in NOX2(-/-) mice.
  
  
  CONCLUSIONS
  Our findings suggest that the angiogenic effects of leptin involve sca-1(+), flk-1(+) vascular progenitor cells mobilized from the BM in response to ObR-mediated activation of NOX2, increased MMP9 expression, and sKitL release.
authors: Department of Cardiology and Pulmonary Medicine, Georg August University of Goettingen, Germany.
authors: Marco R
authors: MR
authors: Schroeter
authors: Susanne
authors: S
authors: Stein
authors: Nana-Maria
authors: NM
authors: Heida
authors: Maren
authors: M
authors: Leifheit-Nestler
authors: I-Fen
authors: IF
authors: Cheng
authors: Rajinikanth
authors: R
authors: Gogiraju
authors: Hans
authors: H
authors: Christiansen
authors: Lars S
authors: LS
authors: Maier
authors: Ajay M
authors: AM
authors: Shah
authors: Gerd
authors: G
authors: Hasenfuss
authors: Stavros
authors: S
authors: Konstantinides
authors: Katrin
authors: K
authors: Schäfer
mesh_terms: D000818:Animals; D016026:Bone Marrow Transplantation; D004789:Enzyme Activation; D006412:Hematopoietic Stem Cells / Q000187:drug effects* / Q000502:physiology; D006614:Hindlimb / Q000098:blood supply; D007511:Ischemia / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D020738:Leptin / Q000008:administration & dosage / Q000494:pharmacology* / Q000502:physiology; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D054411:Receptors, Leptin / Q000172:deficiency / Q000235:genetics; D019089:Stem Cell Factor / Q000097:blood
chemical_list: D020738:Leptin; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D054411:Receptors, Leptin; D019089:Stem Cell Factor; C515447:leptin receptor, mouse; C488842:Cybb protein, mouse; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases; D020780:Matrix Metalloproteinase 9; C501830:Mmp9 protein, mouse