PMID- 11909815
OWN - NLM
STAT- MEDLINE
DCOM- 20020326
LR  - 20220409
IS  - 1524-4571 (Electronic)
IS  - 0009-7330 (Linking)
VI  - 90
IP  - 5
DP  - 2002 Mar 22
TI  - Matrix metalloproteinases: regulation and dysregulation in the failing heart.
PG  - 520-30
AB  - Matrix metalloproteinases (MMPs) are a family of proteolytic enzymes responsible 
      for myocardial extracellular protein degradation. Several MMP species identified 
      within the human myocardium may be dysregulated in congestive heart failure 
      (CHF). For example, MMPs that are expressed at very low levels in normal 
      myocardium, such as collagenase-3 (MMP-13) and the membrane-type-1 MMPs, are 
      substantially upregulated in CHF. However, MMP species are not uniformly 
      increased in patients with end-stage CHF, suggesting that a specific portfolio of 
      MMPs are expressed in the failing myocardium. With the use of animal models of 
      CHF, a mechanistic relationship has been demonstrated with respect to myocardial 
      MMP expression and the left ventricular (LV) remodeling process. The tissue 
      inhibitors of the MMPs (TIMPs) are locally synthesized proteins that bind to 
      active MMPs and thereby regulate net proteolytic activity. However, there does 
      not appear to be a concomitant increase in myocardial TIMPs during the LV 
      remodeling process and progression to CHF. This disparity between MMP and TIMP 
      levels favors a persistent MMP activation state within the myocardium and likely 
      contributes to the LV remodeling process in the setting of developing CHF. The 
      elucidation of upstream signaling mechanisms that contribute to the selective 
      induction of MMP species within the myocardium as well as strategies to normalize 
      the balance between MMPs and TIMPs may yield some therapeutic strategies by which 
      to control myocardial extracellular remodeling and thereby slow the progression 
      of the CHF process.
FAU - Spinale, Francis G
AU  - Spinale FG
AD  - Cardiothoracic Surgery, Medical University of South Carolina, Charleston 29425, 
      USA.
LA  - eng
GR  - HL-45024/HL/NHLBI NIH HHS/United States
GR  - HL-97012/HL/NHLBI NIH HHS/United States
GR  - P01 HL-48788/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PT  - Review
PL  - United States
TA  - Circ Res
JT  - Circulation research
JID - 0047103
RN  - 0 (Tissue Inhibitor of Metalloproteinases)
RN  - EC 3.4.24.- (Matrix Metalloproteinases)
SB  - IM
MH  - Animals
MH  - Disease Models, Animal
MH  - Feedback, Physiological
MH  - Heart Failure/*enzymology
MH  - Humans
MH  - Matrix Metalloproteinases/*metabolism
MH  - Myocardium/enzymology
MH  - Signal Transduction
MH  - Tissue Inhibitor of Metalloproteinases/metabolism
MH  - Ventricular Remodeling
RF  - 88
EDAT- 2002/03/23 10:00
MHDA- 2002/03/27 10:01
CRDT- 2002/03/23 10:00
PHST- 2002/03/23 10:00 [pubmed]
PHST- 2002/03/27 10:01 [medline]
PHST- 2002/03/23 10:00 [entrez]
AID - 10.1161/01.res.0000013290.12884.a3 [doi]
PST - ppublish
SO  - Circ Res. 2002 Mar 22;90(5):520-30. doi: 10.1161/01.res.0000013290.12884.a3.