PMID- 19494241
OWN - NLM
STAT- MEDLINE
DCOM- 20090921
LR  - 20211020
IS  - 1522-1563 (Electronic)
IS  - 0363-6143 (Print)
IS  - 0363-6143 (Linking)
VI  - 297
IP  - 2
DP  - 2009 Aug
TI  - Vascular regression and survival are differentially regulated by MT1-MMP and 
      TIMPs in the aortic ring model of angiogenesis.
PG  - C471-80
LID - 10.1152/ajpcell.00019.2009 [doi]
AB  - This study was designed to investigate the role of matrix metalloproteinases 
      (MMPs) and tissue inhibitors of MMPs (TIMPs) in the reabsorption of neovessels in 
      collagen gel cultures of rat and mouse aortic rings. Aortic angiogenesis was 
      associated with collagen lysis and production of the matrix-degrading enzymes 
      MMP-2, MMP-9, and membrane-type MMP (MT1-MMP, or MMP-14). Vascular growth and 
      regression were not affected by disruption of MMP-2 or MMP-9. In addition, no 
      effect on vascular regression was observed by blocking plasmin, a protease 
      implicated in the activation of MMPs, with epsilon-aminocaproic acid or by adding 
      plasminogen, which caused a modest increase in vascular proliferation. 
      Conversely, angiogenesis was blocked and vessels stabilized by inhibiting MT1-MMP 
      with neutralizing antibodies, TIMP-2, TIMP-3, or TIMP-4. TIMP-1, which blocks 
      MMP-2 and MMP-9 but is a poor inhibitor of MT1-MMP, had no antiangiogenic effect. 
      However, TIMP-1 prolonged the survival of neovessels following angiogenesis. 
      Vascular regression was accelerated in aortic cultures from TIMP-1- and 
      TIMP-2-deficient mice. The vascular survival effect of anti-MT1-MMP antibodies 
      and TIMPs with MT1-MMP inhibitory activity was associated with complete 
      inhibition of collagen lysis. In contrast, TIMP-1 had no anticollagenolytic 
      effect. These results indicate that MT1-MMP plays a critical role not only in 
      angiogenesis but also in vascular regression and demonstrate that TIMPs with 
      anti-MT1-MMP activity have opposite effects on angiogenic outcomes depending on 
      the stage of the angiogenic process. This study also suggests the existence of a 
      TIMP-1-mediated alternate pathway of vascular survival that is unrelated to 
      MT1-MMP inhibitory activity.
FAU - Aplin, A C
AU  - Aplin AC
AD  - Department of Pathology, University of Washington, Seattle, WA, USA.
FAU - Zhu, W H
AU  - Zhu WH
FAU - Fogel, E
AU  - Fogel E
FAU - Nicosia, R F
AU  - Nicosia RF
LA  - eng
GR  - HL52585/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20090603
PL  - United States
TA  - Am J Physiol Cell Physiol
JT  - American journal of physiology. Cell physiology
JID - 100901225
RN  - 0 (Antifibrinolytic Agents)
RN  - 0 (Protein Isoforms)
RN  - 0 (Tissue Inhibitor of Metalloproteinases)
RN  - 9001-91-6 (Plasminogen)
RN  - EC 3.4.21.7 (Fibrinolysin)
RN  - EC 3.4.24.24 (Matrix Metalloproteinase 2)
RN  - EC 3.4.24.35 (Matrix Metalloproteinase 9)
RN  - EC 3.4.24.80 (Matrix Metalloproteinase 14)
RN  - U6F3787206 (Aminocaproic Acid)
SB  - IM
MH  - Aminocaproic Acid/metabolism
MH  - Animals
MH  - Antifibrinolytic Agents/metabolism
MH  - *Aorta/anatomy & histology/metabolism
MH  - Fibrinolysin/metabolism
MH  - Humans
MH  - Matrix Metalloproteinase 14/*metabolism
MH  - Matrix Metalloproteinase 2/genetics/metabolism
MH  - Matrix Metalloproteinase 9/genetics/metabolism
MH  - Mice
MH  - *Neovascularization, Physiologic
MH  - Plasminogen/metabolism
MH  - Protein Isoforms/genetics/*metabolism
MH  - Rats
MH  - Tissue Culture Techniques
MH  - Tissue Inhibitor of Metalloproteinases/genetics/*metabolism
PMC - PMC2724089
EDAT- 2009/06/06 09:00
MHDA- 2009/09/22 06:00
PMCR- 2010/08/01
CRDT- 2009/06/05 09:00
PHST- 2009/06/05 09:00 [entrez]
PHST- 2009/06/06 09:00 [pubmed]
PHST- 2009/09/22 06:00 [medline]
PHST- 2010/08/01 00:00 [pmc-release]
AID - 00019.2009 [pii]
AID - C-00019-2009 [pii]
AID - 10.1152/ajpcell.00019.2009 [doi]
PST - ppublish
SO  - Am J Physiol Cell Physiol. 2009 Aug;297(2):C471-80. doi: 
      10.1152/ajpcell.00019.2009. Epub 2009 Jun 3.