PMID- 15680392
OWN - NLM
STAT- MEDLINE
DCOM- 20050321
LR  - 20151119
IS  - 0022-4804 (Print)
IS  - 0022-4804 (Linking)
VI  - 123
IP  - 2
DP  - 2005 Feb
TI  - Enhanced abdominal aortic aneurysm in TIMP-1-deficient mice.
PG  - 289-93
AB  - BACKGROUND: Matrix metalloproteinases (MMPs) are known elastolytic mediators of 
      abdominal aortic aneurysm (AAA) degeneration, and their activity is tightly 
      regulated by the presence of tissue inhibitors of MMPs (TIMPs). Imbalances in 
      this system may be instrumental in compromising arterial wall integrity. The aim 
      of this study was to show that, in an elastase-induced murine model of aneurysm 
      formation, TIMP-1 has a protective effect. MATERIALS AND METHODS: Twenty-four 
      wild-type (TIMP-1+/+) and 22 knockout (TIMP-1-/-) mice underwent laparotomy and 
      isolation of the infrarenal aorta. A polyethylene catheter was inserted into the 
      aorta and dilute pancreatic elastase (0.39 Units/ml) was infused over 5 min using 
      a perfusion pump. Pre- and postinfusion maximal aortic diameters were obtained in 
      triplicate for each animal using NIH Image. Final aortic measurements were 
      obtained 14 days later, prior to perfusion fixation with 10% buffered Formalin. 
      Aortic specimens were sectioned and stained. Statistical analysis was performed 
      using the Student's t test. RESULTS: TIMP-1-/- mice demonstrated a significant 
      postinfusion diameter increase compared to wild-types after elastase, which was 
      not seen after saline infusion. At sacrifice, TIMP-1-/- mice, following both 
      saline and elastase infusion, showed a significant increase in maximal aortic 
      diameter relative to postinfusion measurements compared to TIMP-1+/+ mice. 
      CONCLUSIONS: TIMP-1-/- mice develop larger aneurysms than TIMP-1+/+ mice. This 
      study illustrates the protective effects of TIMP-1 in an experimental AAA model 
      and may provide a means for pharmacologically controlling aneurysm growth.
FAU - Eskandari, Mark K
AU  - Eskandari MK
AD  - Division of Vascular Surgery, Feinberg School of Medicine, Northwestern 
      University, Chicago, Illinois, USA. meskanda@nmh.org
FAU - Vijungco, Joseph D
AU  - Vijungco JD
FAU - Flores, Amy
AU  - Flores A
FAU - Borensztajn, Jayme
AU  - Borensztajn J
FAU - Shively, Vera
AU  - Shively V
FAU - Pearce, William H
AU  - Pearce WH
LA  - eng
PT  - Journal Article
PL  - United States
TA  - J Surg Res
JT  - The Journal of surgical research
JID - 0376340
RN  - 0 (Tissue Inhibitor of Metalloproteinase-1)
RN  - 451W47IQ8X (Sodium Chloride)
RN  - EC 3.4.21.36 (Pancreatic Elastase)
SB  - IM
MH  - Animals
MH  - Aorta, Abdominal/pathology
MH  - Aortic Aneurysm, Abdominal/chemically induced/pathology/*physiopathology
MH  - Disease Models, Animal
MH  - Female
MH  - Male
MH  - Mice
MH  - Mice, Knockout
MH  - Pancreatic Elastase
MH  - Severity of Illness Index
MH  - Sodium Chloride
MH  - Tissue Inhibitor of Metalloproteinase-1/*genetics/*physiology
EDAT- 2005/02/01 09:00
MHDA- 2005/03/22 09:00
CRDT- 2005/02/01 09:00
PHST- 2004/07/01 00:00 [received]
PHST- 2005/02/01 09:00 [pubmed]
PHST- 2005/03/22 09:00 [medline]
PHST- 2005/02/01 09:00 [entrez]
AID - S0022-4804(04)00523-2 [pii]
AID - 10.1016/j.jss.2004.07.247 [doi]
PST - ppublish
SO  - J Surg Res. 2005 Feb;123(2):289-93. doi: 10.1016/j.jss.2004.07.247.