PMID- 10773234
OWN - NLM
STAT- MEDLINE
DCOM- 20000612
LR  - 20231213
IS  - 0008-6363 (Print)
IS  - 0008-6363 (Linking)
VI  - 46
IP  - 2
DP  - 2000 May
TI  - MMP/TIMP expression in spontaneously hypertensive heart failure rats: the effect 
      of ACE- and MMP-inhibition.
PG  - 298-306
AB  - OBJECTIVE: Determine the effect of a matrix metalloproteinase inhibitor (MMPi) 
      and angiotensin converting enzyme inhibitor (ACEi) on collagen, MMP, tissue 
      inhibitors of MMPs (TIMPs) expression in the spontaneously hypertensive heart 
      failure (SHHF) rat. METHODS: Six groups were tested: normotensive 9- and 
      13-month-old Wistar-Furth (WF) rats, 9-month-old SHHFs (compensatory 
      hypertrophy), 13-month-old SHHFs with HF, and 13-month-old SHHFs orally 
      administered with either an MMPi (PD166793, 5 mgkg(-1)day(-1)) or ACEi 
      (quinapril, 10 mgkg(-1)day(-1)) for 4 months. Collagen volume fraction was 
      assessed histomorphometrically. Left ventricular (LV) mRNA 
      [MMP-1,-2,-3,-7,-9,-11,-13,-14; TIMP-1,-2,-3,-4; and collagen alpha1(I) and 
      alpha1(III)] and protein (MMP-2 and MMP-9 zymographic activity; Western blot 
      analysis of MMP-13, and TIMP-1,-2,-4) levels could be quantified. RESULTS: 
      Collagen mRNA levels were elevated in SHHFs compared to age-matched controls, but 
      collagen volume fraction was elevated only in 13-month-old SHHFs (approximately 
      2x). Only MMP-2 mRNA levels increased significantly with HF. However, MMP-2 and 
      MMP-9 zymographic activity, and MMP-13 protein levels increased. TIMP-1 and 
      TIMP-2 mRNA and protein levels increased, and TIMP-4 protein levels decreased in 
      SHHFs vs. controls. Both drug treatments reduced LV dilation; preserved systolic 
      function; and normalized MMP/TIMP expression. Both drug treatments also reduced 
      collagen volume fraction, but only quinapril reduced collagen mRNA levels and LV 
      hypertrophy. CONCLUSIONS: The divergent effect of MMPi and ACEi on collagen mRNA 
      levels and hypertrophy indicate that drug efficacy is mediated by different 
      pathways in the SHHF rat.
FAU - Li, H
AU  - Li H
AD  - Department of Cardiovascular Therapeutics, Parke-Davis Pharmaceutical Research, 
      Division of Warner-Lambert Company, 2800 Plymouth Road, Ann Arbor, MI 48105, USA.
FAU - Simon, H
AU  - Simon H
FAU - Bocan, T M
AU  - Bocan TM
FAU - Peterson, J T
AU  - Peterson JT
LA  - eng
PT  - Journal Article
PL  - England
TA  - Cardiovasc Res
JT  - Cardiovascular research
JID - 0077427
RN  - 0 ((R)-2-(4'-bromo-biphenyl-4-sulfonyl-amino)-3-methyl-butyric acid)
RN  - 0 (Angiotensin-Converting Enzyme Inhibitors)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Hydroxamic Acids)
RN  - 0 (Isoquinolines)
RN  - 0 (Matrix Metalloproteinase Inhibitors)
RN  - 0 (Oligopeptides)
RN  - 0 (Tetrahydroisoquinolines)
RN  - 0 (Tissue Inhibitor of Metalloproteinase-1)
RN  - 0 (Tissue Inhibitor of Metalloproteinases)
RN  - 127497-59-0 (Tissue Inhibitor of Metalloproteinase-2)
RN  - 9007-34-5 (Collagen)
RN  - EC 3.4.24.- (Collagenases)
RN  - EC 3.4.24.- (Matrix Metalloproteinase 13)
RN  - EC 3.4.24.- (Matrix Metalloproteinases)
RN  - EC 3.4.24.- (Mmp13 protein, rat)
RN  - EC 3.4.24.24 (Matrix Metalloproteinase 2)
RN  - EC 3.4.24.35 (Matrix Metalloproteinase 9)
RN  - RJ84Y44811 (Quinapril)
SB  - IM
MH  - Analysis of Variance
MH  - Angiotensin-Converting Enzyme Inhibitors/therapeutic use
MH  - Animals
MH  - Blotting, Northern/methods
MH  - Blotting, Western/methods
MH  - Collagen/analysis
MH  - Collagenases/analysis/metabolism
MH  - Enzyme Inhibitors/therapeutic use
MH  - Heart Failure/drug therapy/*enzymology
MH  - Hydroxamic Acids/therapeutic use
MH  - Isoquinolines/therapeutic use
MH  - Male
MH  - Matrix Metalloproteinase 13
MH  - Matrix Metalloproteinase 2/analysis/metabolism
MH  - Matrix Metalloproteinase 9/analysis/metabolism
MH  - Matrix Metalloproteinase Inhibitors
MH  - Matrix Metalloproteinases/analysis/*metabolism
MH  - Myocardium/chemistry/*enzymology
MH  - Oligopeptides/therapeutic use
MH  - Quinapril
MH  - Rats
MH  - Rats, Inbred SHR
MH  - Rats, Inbred WF
MH  - *Tetrahydroisoquinolines
MH  - Tissue Inhibitor of Metalloproteinase-1/analysis/metabolism
MH  - Tissue Inhibitor of Metalloproteinase-2/analysis/metabolism
MH  - Tissue Inhibitor of Metalloproteinases/analysis/*metabolism
MH  - Tissue Inhibitor of Metalloproteinase-4
EDAT- 2000/04/25 09:00
MHDA- 2000/06/17 09:00
CRDT- 2000/04/25 09:00
PHST- 2000/04/25 09:00 [pubmed]
PHST- 2000/06/17 09:00 [medline]
PHST- 2000/04/25 09:00 [entrez]
AID - S0008-6363(00)00028-6 [pii]
AID - 10.1016/s0008-6363(00)00028-6 [doi]
PST - ppublish
SO  - Cardiovasc Res. 2000 May;46(2):298-306. doi: 10.1016/s0008-6363(00)00028-6.