PMID- 15976330
OWN - NLM
STAT- MEDLINE
DCOM- 20060106
LR  - 20111102
IS  - 1524-4636 (Electronic)
IS  - 1079-5642 (Linking)
VI  - 25
IP  - 9
DP  - 2005 Sep
TI  - Important role of apoptosis signal-regulating kinase 1 in ischemia-induced 
      angiogenesis.
PG  - 1877-83
AB  - OBJECTIVE: We first examined the role of apoptosis signal-regulating kinase 1 
      (ASK1), one of mitogen-activated protein kinase kinase kinases, in 
      ischemia-induced angiogenesis. METHODS AND RESULTS: Unilateral hindlimb ischemia 
      was induced surgically in C57BL/6J wild-type (WT) mice or mice deficient in ASK1 
      (ASK1(-/-)). ASK1 activity in WT mouse hindlimb was increased dramatically after 
      ischemia. By laser Doppler analysis, well-developed collateral vessels and 
      angiogenesis were observed in WT mice in response to hindlimb ischemia, whereas 
      these responses were reduced in ASK1(-/-) mice. Immunostaining revealed that 
      infiltration of macrophages and T lymphocytes was suppressed in the ischemic 
      tissues of ASK1(-/-) mice compared with WT mice. The expression of vascular 
      endothelial growth factor (VEGF) and monocyte chemoattractant protein-1 (MCP-1) 
      proteins in ischemic tissues was weaker in ASK1(-/-) mice compared with WT mice. 
      In vitro study on endothelial cells indicated that dominant-negative ASK1 
      significantly attenuated hydrogen peroxide-induced VEGF and MCP-1 production. 
      Furthermore, in vivo blockade of MCP-1 by its neutralizing antibody suppressed 
      the recovery of the blood flow and capillary formation after ischemia. 
      CONCLUSIONS: ASK1 pathway promotes early angiogenesis by inducing inflammatory 
      cell infiltration and VEGF and MCP-1 expression. ASK1 may provide the basis for 
      the development of new therapeutic strategy for angiogenesis.
FAU - Izumi, Yasukatsu
AU  - Izumi Y
AD  - Department of Pharmacology, Osaka City University Medical School, Japan.
FAU - Kim-Mitsuyama, Shokei
AU  - Kim-Mitsuyama S
FAU - Yoshiyama, Minoru
AU  - Yoshiyama M
FAU - Omura, Takashi
AU  - Omura T
FAU - Shiota, Masayuki
AU  - Shiota M
FAU - Matsuzawa, Atsushi
AU  - Matsuzawa A
FAU - Yukimura, Tokihito
AU  - Yukimura T
FAU - Murohara, Toyoaki
AU  - Murohara T
FAU - Takeya, Motohiro
AU  - Takeya M
FAU - Ichijo, Hidenori
AU  - Ichijo H
FAU - Yoshikawa, Junichi
AU  - Yoshikawa J
FAU - Iwao, Hiroshi
AU  - Iwao H
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20050623
PL  - United States
TA  - Arterioscler Thromb Vasc Biol
JT  - Arteriosclerosis, thrombosis, and vascular biology
JID - 9505803
RN  - 0 (Ccl2 protein, mouse)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Vascular Endothelial Growth Factor A)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
RN  - EC 2.7.11.25 (MAP Kinase Kinase Kinase 5)
RN  - EC 2.7.11.25 (Map3k5 protein, mouse)
SB  - IM
MH  - Animals
MH  - Capillaries/physiology
MH  - Chemokine CCL2/antagonists & inhibitors/metabolism
MH  - Disease Models, Animal
MH  - Endothelium, Vascular/cytology/immunology/metabolism
MH  - Hindlimb/blood supply
MH  - Humans
MH  - Ischemia/*immunology/*metabolism
MH  - MAP Kinase Kinase Kinase 5/*genetics/*metabolism
MH  - Macrophages/immunology
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Mutant Strains
MH  - Mitogen-Activated Protein Kinases/metabolism
MH  - Neovascularization, Physiologic/*physiology
MH  - T-Lymphocytes/immunology
MH  - Umbilical Veins/cytology
MH  - Vascular Endothelial Growth Factor A/metabolism
EDAT- 2005/06/25 09:00
MHDA- 2006/01/07 09:00
CRDT- 2005/06/25 09:00
PHST- 2005/06/25 09:00 [pubmed]
PHST- 2006/01/07 09:00 [medline]
PHST- 2005/06/25 09:00 [entrez]
AID - 01.ATV.0000174801.76234.bd [pii]
AID - 10.1161/01.ATV.0000174801.76234.bd [doi]
PST - ppublish
SO  - Arterioscler Thromb Vasc Biol. 2005 Sep;25(9):1877-83. doi: 
      10.1161/01.ATV.0000174801.76234.bd. Epub 2005 Jun 23.