PMID- 10652195
OWN - NLM
STAT- MEDLINE
DCOM- 20000418
LR  - 20071114
IS  - 0022-2828 (Print)
IS  - 0022-2828 (Linking)
VI  - 32
IP  - 1
DP  - 2000 Jan
TI  - Effects of gene deletion of the tissue inhibitor of the matrix 
      metalloproteinase-type 1 (TIMP-1) on left ventricular geometry and function in 
      mice.
PG  - 109-20
AB  - Alterations in the expression and activity of the matrix metalloproteinases 
      (MMPs) and the tissue inhibitors of the MMPs (TIMPs) have been implicated in 
      tissue remodeling in a number of disease states. One of the better characterized 
      TIMPs, TIMP-1, has been shown to bind to active MMPs and to regulate the MMP 
      activational process. The goal of this study was to determine whether deletion of 
      the TIMP-1 gene in mice, which in turn would remove TIMP-1 expression in LV 
      myocardium, would produce time-dependent effects on LV geometry and function. 
      Age-matched sibling mice (129Sv) deficient in the TIMP-1 gene (TIMP-1 knock-out 
      (TIMP-1 KO), n=10) and wild-type mice (n=10) underwent comparative 
      echocardiographic studies at 1 and 4 months of age. LV catheterization studies 
      were performed at 4 months and the LV harvested for histomorphometric studies. LV 
      end-diastolic volume and mass increased (18+/-4 and 38+/-3%, respectively, 
      P<0.05) at 4 months in the TIMP-1 KO group; a significant increase compared to 
      wild-type controls (P<0.05). At 4 months, LV and end-diastolic wall stress was 
      increased by over two-fold in the TIMP-1 KO compared to wild type (P<0.05). 
      However, LV systolic pressure and ejection performance were unchanged in the two 
      groups of mice. LV myocyte cross-sectional area was unchanged in the TIMP-1 KO 
      mice compared to controls, but myocardial fibrillar collagen content was reduced. 
      Changes in LV geometry occurred in TIMP-1 deficient mice and these results 
      suggest that constitutive TIMP-1 expression participates in the maintenance of 
      normal LV myocardial structure.
CI  - Copyright 2000 Academic Press.
FAU - Roten, L
AU  - Roten L
AD  - Division of Cardiothoracic Surgery and Cardiology, Medical University of South 
      Carolina and Roswell Park Cancer Institute, Buffalo, New York, USA.
FAU - Nemoto, S
AU  - Nemoto S
FAU - Simsic, J
AU  - Simsic J
FAU - Coker, M L
AU  - Coker ML
FAU - Rao, V
AU  - Rao V
FAU - Baicu, S
AU  - Baicu S
FAU - Defreyte, G
AU  - Defreyte G
FAU - Soloway, P J
AU  - Soloway PJ
FAU - Zile, M R
AU  - Zile MR
FAU - Spinale, F G
AU  - Spinale FG
LA  - eng
GR  - HL-57952/HL/NHLBI NIH HHS/United States
GR  - HL-59165/HL/NHLBI NIH HHS/United States
GR  - P01 HL48788/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - England
TA  - J Mol Cell Cardiol
JT  - Journal of molecular and cellular cardiology
JID - 0262322
RN  - 0 (Tissue Inhibitor of Metalloproteinase-1)
RN  - 9007-34-5 (Collagen)
SB  - IM
MH  - Animals
MH  - Cell Count
MH  - Collagen/metabolism
MH  - Gene Deletion
MH  - Heart/*physiology
MH  - Heart Ventricles
MH  - Mice
MH  - Mice, Knockout
MH  - Microtomy
MH  - Myocardium/metabolism/pathology
MH  - Tissue Inhibitor of Metalloproteinase-1/genetics/*physiology
OTO - NASA
OT  - NASA Discipline Cardiopulmonary
OT  - NASA Program Biomedical Research and Countermeasures
OT  - Non-NASA Center
FIR - Zile, M R
IR  - Zile MR
IRAD- Med U SC, Charleston
EDAT- 2000/02/01 09:00
MHDA- 2000/04/25 09:00
CRDT- 2000/02/01 09:00
PHST- 2000/02/01 09:00 [pubmed]
PHST- 2000/04/25 09:00 [medline]
PHST- 2000/02/01 09:00 [entrez]
AID - S0022-2828(99)91052-0 [pii]
AID - 10.1006/jmcc.1999.1052 [doi]
PST - ppublish
SO  - J Mol Cell Cardiol. 2000 Jan;32(1):109-20. doi: 10.1006/jmcc.1999.1052.