PMID- 17261656
OWN - NLM
STAT- MEDLINE
DCOM- 20070312
LR  - 20081121
IS  - 1524-4539 (Electronic)
IS  - 0009-7322 (Linking)
VI  - 115
IP  - 6
DP  - 2007 Feb 13
TI  - Tumor necrosis factor-alpha receptor p75 is required in ischemia-induced 
      neovascularization.
PG  - 752-62
AB  - BACKGROUND: Aging is a risk factor for coronary and peripheral artery disease. 
      Tumor necrosis factor-alpha (TNF-alpha), a proinflammatory cytokine, is expressed 
      in ischemic tissue and is known to modulate angiogenesis. Little is known about 
      the role of TNF-alpha receptors (TNFR1/p55 and TNFR2/p75) in angiogenic 
      signaling. METHODS AND RESULTS: We studied neovascularization in the hindlimb 
      ischemia model in young and old TNFR2/p75 knockout (p75KO) and wild-type 
      age-matched controls. Between days 7 to 10 after hindlimb surgery, 100% of old 
      p75KOs experienced autoamputation of the operated limbs, whereas none of the 
      age-matched wild-type mice exhibited hindlimb necrosis. Poor blood flow recovery 
      in p75KO mice was associated with increased endothelial cell apoptosis, decreased 
      capillary density, and significant reductions in the expression of vascular 
      endothelial growth factor and basic fibroblast growth factor-2 mRNA transcripts 
      in ischemic tissue and in circulating endothelial progenitor cells. The number of 
      circulating bone marrow-derived endothelial progenitor cells was significantly 
      reduced in p75KO mice. Transplantation of wild-type bone marrow mononuclear cells 
      into irradiated old p75KO mice 1 month before hindlimb surgery prevented limb 
      loss. CONCLUSIONS: Our present study suggests that ischemia-induced endothelial 
      progenitor cell-mediated neovascularization is dependent, at least in part, on 
      p75 TNF receptor expressed in bone marrow-derived cells. Specifically, 
      endothelial cell/endothelial progenitor cell survival, vascular endothelial 
      growth factor expression, endothelial progenitor cell mobilization from bone 
      marrow, endothelial progenitor cell differentiation, and ultimately 
      ischemia-induced collateral vessel development are dependent on signaling through 
      TNFR2/p75. Furthermore, because TNFR2/p75 becomes an age-related limiting factor 
      in postischemic recovery, it may be a potential gene target for therapeutic 
      interventions in adult vascular diseases.
FAU - Goukassian, David A
AU  - Goukassian DA
AD  - Division of Cardiovascular Diseases, Department of Medicine, Caritas St 
      Elizabeth's Medical Center, Boston, Mass, USA. dgoukass@bu.edu
FAU - Qin, Gangjian
AU  - Qin G
FAU - Dolan, Christine
AU  - Dolan C
FAU - Murayama, Toshinori
AU  - Murayama T
FAU - Silver, Marcy
AU  - Silver M
FAU - Curry, Cynthia
AU  - Curry C
FAU - Eaton, Elizabeth
AU  - Eaton E
FAU - Luedemann, Corinne
AU  - Luedemann C
FAU - Ma, Hong
AU  - Ma H
FAU - Asahara, Takayuki
AU  - Asahara T
FAU - Zak, Victor
AU  - Zak V
FAU - Mehta, Shanu
AU  - Mehta S
FAU - Burg, Aaron
AU  - Burg A
FAU - Thorne, Tina
AU  - Thorne T
FAU - Kishore, Raj
AU  - Kishore R
FAU - Losordo, Douglas W
AU  - Losordo DW
LA  - eng
GR  - HL-53354/HL/NHLBI NIH HHS/United States
GR  - HL-57516/HL/NHLBI NIH HHS/United States
GR  - HL-63414/HL/NHLBI NIH HHS/United States
GR  - HL-77428/HL/NHLBI NIH HHS/United States
GR  - HL-80137/HL/NHLBI NIH HHS/United States
GR  - P01HL-66957/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20070129
PL  - United States
TA  - Circulation
JT  - Circulation
JID - 0147763
RN  - 0 (NF-kappa B)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, Tumor Necrosis Factor, Type II)
RN  - 0 (Vascular Endothelial Growth Factor A)
SB  - IM
MH  - Aging/physiology
MH  - Animals
MH  - Apoptosis
MH  - Bone Marrow Transplantation
MH  - Cells, Cultured
MH  - Endothelial Cells/pathology
MH  - Hindlimb/blood supply
MH  - Ischemia/*physiopathology
MH  - Mice
MH  - Mice, Knockout
MH  - NF-kappa B/metabolism
MH  - *Neovascularization, Physiologic
MH  - Promoter Regions, Genetic
MH  - RNA, Messenger/analysis
MH  - Receptors, Tumor Necrosis Factor, Type II/*physiology
MH  - Signal Transduction
MH  - Stem Cells/physiology
MH  - Vascular Endothelial Growth Factor A/genetics
EDAT- 2007/01/31 09:00
MHDA- 2007/03/14 09:00
CRDT- 2007/01/31 09:00
PHST- 2007/01/31 09:00 [pubmed]
PHST- 2007/03/14 09:00 [medline]
PHST- 2007/01/31 09:00 [entrez]
AID - CIRCULATIONAHA.106.647255 [pii]
AID - 10.1161/CIRCULATIONAHA.106.647255 [doi]
PST - ppublish
SO  - Circulation. 2007 Feb 13;115(6):752-62. doi: 10.1161/CIRCULATIONAHA.106.647255. 
      Epub 2007 Jan 29.