PMID- 10937974
OWN - NLM
STAT- MEDLINE
DCOM- 20000830
LR  - 20110608
IS  - 1388-9842 (Print)
IS  - 1388-9842 (Linking)
VI  - 1
IP  - 1
DP  - 1999 Mar
TI  - Novel approaches to retard ventricular remodeling in heart failure.
PG  - 17-23
AB  - While the etiologies of congestive heart failure (CHF) are diverse, a common 
      event in the progression of this disease process is LV remodeling, increased wall 
      stress, and subsequent pump dysfunction. Therapeutic approaches for CHF have been 
      focused upon reducing LV afterload through vasodilator therapy, or by 
      blocking/interrupting the effects of neurohormonal stimuli. However, another 
      therapeutic approach would be to directly intervene in the LV remodeling process 
      with CHF. An important determinant in the maintenance of myocyte shape, alignment 
      and transduction of myocyte shortening into an overall ejection is the structural 
      support provided by the fibrillar collagen matrix. As in most tissue remodeling 
      processes, LV myocardial remodeling with CHF is accompanied by changes in the 
      structure and composition of the collagen matrix. Matrix metalloproteinases 
      (MMPs) are an endogenous family of zinc-dependent enzymes which have been 
      identified to be responsible for matrix remodeling and alterations in MMP 
      expression and activity have been identified in clinical and animal models of 
      CHF. Moreover, alterations in the tissue inhibitors of MMPs (TIMPs) have also 
      been identified to occur in the end-stage CHF myocardium. Thus, it is very likely 
      that increased MMP activity and reduced inhibitory control of the TIMPs 
      contribute to the LV remodeling process with CHF. A number of bioactive peptides 
      and cytokines influence MMP and TIMP expression and activity. In addition, 
      pharmacologically active MMP inhibitors have been synthesized and are currently 
      under study. Accordingly, the control of MMP and TIMP expression and activity 
      within the failing myocardium represents a new and potentially significant 
      therapeutic target for CHF.
FAU - Spinale, F G
AU  - Spinale FG
LA  - eng
GR  - HL97-012/HL/NHLBI NIH HHS/United States
PT  - Editorial
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - England
TA  - Eur J Heart Fail
JT  - European journal of heart failure
JID - 100887595
RN  - 0 (Tissue Inhibitor of Metalloproteinases)
RN  - EC 3.4.24.- (Matrix Metalloproteinases)
RN  - EC 3.4.24.17 (Matrix Metalloproteinase 3)
RN  - EC 3.4.24.7 (Matrix Metalloproteinase 1)
SB  - IM
MH  - Heart Failure/metabolism/*physiopathology
MH  - Humans
MH  - Matrix Metalloproteinase 1/metabolism
MH  - Matrix Metalloproteinase 3/metabolism
MH  - Matrix Metalloproteinases/*metabolism
MH  - Tissue Inhibitor of Metalloproteinases/metabolism
MH  - *Ventricular Remodeling
EDAT- 2000/08/11 11:00
MHDA- 2000/09/02 11:01
CRDT- 2000/08/11 11:00
PHST- 2000/08/11 11:00 [pubmed]
PHST- 2000/09/02 11:01 [medline]
PHST- 2000/08/11 11:00 [entrez]
AID - S1388-9842(98)00012-9 [pii]
AID - 10.1016/S1388-9842(98)00012-9 [doi]
PST - ppublish
SO  - Eur J Heart Fail. 1999 Mar;1(1):17-23. doi: 10.1016/S1388-9842(98)00012-9.