PMID- 9591765
OWN - NLM
STAT- MEDLINE
DCOM- 19980528
LR  - 20220316
IS  - 0009-7322 (Print)
IS  - 0009-7322 (Linking)
VI  - 97
IP  - 17
DP  - 1998 May 5
TI  - Increased matrix metalloproteinase activity and selective upregulation in LV 
      myocardium from patients with end-stage dilated cardiomyopathy.
PG  - 1708-15
AB  - BACKGROUND: One of the hallmarks of dilated cardiomyopathy (DCM) is left 
      ventricular (LV) remodeling. The matrix metalloproteinases (MMPs) are a family of 
      enzymes that contribute to extracellular remodeling in several disease states. 
      Additionally, a family of inhibitors called tissue inhibitors of MMPs (TIMPs) has 
      been shown to exist and to tightly regulate MMP activity. However, the types of 
      MMPs and TIMPs expressed within the normal and DCM LV myocardium and the relation 
      to MMP activity remain unexplored. METHODS AND RESULTS: Relative LV myocardial 
      MMP activity was determined in the normal (n=8) and idiopathic DCM (n=7) human LV 
      myocardium by substrate zymography. Relative LV myocardial abundance of 
      interstitial collagenase (MMP-1), stromelysin (MMP-3), 72 kD gelatinase (MMP-2), 
      92 kD gelatinase (MMP-9), TIMP-1, and TIMP-2 were measured with quantitative 
      immunoblotting. LV myocardial MMP zymographic activity increased with DCM 
      compared with normal (984+/-149 versus 413+/-64 pixels, P<.05). With DCM, LV 
      myocardial abundance of MMP-1 decreased to 16+/-6% (P<.05), MMP-3 increased to 
      563+/-212% (P<.05), MMP-9 increased to 422+/-64% (P<.05), and MMP-2 was unchanged 
      when compared with normal. LV myocardial abundance of TIMP-1 and TIMP-2 increased 
      by >500% with DCM. A high-molecular-weight immunoreactive band for both TIMP-1 
      and TIMP-2, suggesting a TIMP/MMP complex, was increased >600% with DCM. 
      CONCLUSIONS: This study demonstrated increased LV myocardial MMP activity and 
      evidence for independent regulatory mechanisms of MMP and TIMP expression with 
      DCM. These findings suggest that selective inhibition of MMP species within the 
      LV myocardium may provide a novel therapeutic target in patients with DCM.
FAU - Thomas, C V
AU  - Thomas CV
AD  - Division of Cardiothoracic Surgery, Medical University of South Carolina, 
      Charleston 29425, USA.
FAU - Coker, M L
AU  - Coker ML
FAU - Zellner, J L
AU  - Zellner JL
FAU - Handy, J R
AU  - Handy JR
FAU - Crumbley, A J 3rd
AU  - Crumbley AJ 3rd
FAU - Spinale, F G
AU  - Spinale FG
LA  - eng
GR  - HL-45024/HL/NHLBI NIH HHS/United States
GR  - HL-56603/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  - United States
TA  - Circulation
JT  - Circulation
JID - 0147763
RN  - 0 (Tissue Inhibitor of Metalloproteinase-1)
RN  - 127497-59-0 (Tissue Inhibitor of Metalloproteinase-2)
RN  - EC 3.4.24.- (Collagenases)
RN  - EC 3.4.24.- (Gelatinases)
RN  - EC 3.4.24.- (Metalloendopeptidases)
RN  - EC 3.4.24.17 (Matrix Metalloproteinase 3)
RN  - EC 3.4.24.24 (Matrix Metalloproteinase 2)
RN  - EC 3.4.24.35 (Matrix Metalloproteinase 9)
RN  - EC 3.4.24.7 (Matrix Metalloproteinase 1)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Cardiomyopathy, Dilated/*enzymology
MH  - Child
MH  - Collagenases/*metabolism
MH  - Gelatinases/*metabolism
MH  - Humans
MH  - Immunoblotting
MH  - Matrix Metalloproteinase 1
MH  - Matrix Metalloproteinase 2
MH  - Matrix Metalloproteinase 3/*metabolism
MH  - Matrix Metalloproteinase 9
MH  - Metalloendopeptidases/*metabolism
MH  - Middle Aged
MH  - Myocardium/*enzymology
MH  - Tissue Inhibitor of Metalloproteinase-1/analysis
MH  - Tissue Inhibitor of Metalloproteinase-2/analysis
MH  - Up-Regulation
EDAT- 1998/05/20 02:12
MHDA- 2001/03/28 10:01
CRDT- 1998/05/20 02:12
PHST- 1998/05/20 02:12 [pubmed]
PHST- 2001/03/28 10:01 [medline]
PHST- 1998/05/20 02:12 [entrez]
AID - 10.1161/01.cir.97.17.1708 [doi]
PST - ppublish
SO  - Circulation. 1998 May 5;97(17):1708-15. doi: 10.1161/01.cir.97.17.1708.