PMID- 15470656
OWN - NLM
STAT- MEDLINE
DCOM- 20050623
LR  - 20220223
IS  - 1071-9164 (Print)
IS  - 1071-9164 (Linking)
VI  - 10
IP  - 5
DP  - 2004 Oct
TI  - Improved balance between TIMP-3 and MMP-9 after regional myocardial 
      ischemia-reperfusion during AT1 receptor blockade.
PG  - 442-9
AB  - BACKGROUND: Angiotensin II (AngII) modulates the balance between matrix 
      metalloproteinases (MMPs) and tissue inhibitors of MMPs (TIMPs), and AngII type 1 
      receptor (AT1R) blockers (ARBs) limit left ventricular (LV) dysfunction and 
      remodeling after acute ischemia-reperfusion (IR). Whether ARBs improve TIMP/MMP 
      balance during IR has not been determined. METHODS AND RESULTS: We measured 
      hemodynamics, LV function, MMP-2 and MMP-9, and TIMP-3 and TIMP-4 in the ischemic 
      zone (IZ) and nonischemic zone (NIZ) after in vivo IR (90 minutes anterior 
      ischemia; 120 minutes reperfusion) in 28 dogs that were randomized to sham, IR 
      controls, and IR plus the ARB valsartan. In controls, IR induced LV dysfunction, 
      infarction, and IZ remodeling; increased MMP-9 and decreased TIMP-3 in the IZ 
      compared with the NIZ (low TIMP-3/MMP-9 ratio); and did not change MMP-2 or 
      TIMP-4. Compared with controls, valsartan (1) limited LV dysfunction, infarct 
      size, and IZ remodeling; (2) increased MMP-2 and MMP-9 and TIMP-3 and -4 in the 
      NIZ; and (3) increased TIMP-3 and the TIMP-3/MMP-9 ratio in the IZ, but did not 
      change MMP-2 and TIMP-4. CONCLUSION: Valsartan-induced cardioprotection after IR 
      is associated with enhanced TIMP-3 expression and improved TIMP-3/MMP-9 balance 
      in the in vivo dog model.
FAU - Sawicki, Grzegorz
AU  - Sawicki G
AD  - Cardiovascular Research Group, Division of Cardiology, University of Alberta, 
      Edmonton, Canada.
FAU - Menon, Vijayan
AU  - Menon V
FAU - Jugdutt, Bodh I
AU  - Jugdutt BI
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Card Fail
JT  - Journal of cardiac failure
JID - 9442138
RN  - 0 (Angiotensin II Type 1 Receptor Blockers)
RN  - 0 (Tetrazoles)
RN  - 0 (Tissue Inhibitor of Metalloproteinase-3)
RN  - 80M03YXJ7I (Valsartan)
RN  - EC 3.4.24.24 (Matrix Metalloproteinase 2)
RN  - EC 3.4.24.35 (Matrix Metalloproteinase 9)
RN  - HG18B9YRS7 (Valine)
SB  - IM
MH  - Angiotensin II Type 1 Receptor Blockers/*pharmacology/therapeutic use
MH  - Animals
MH  - Blood Pressure/drug effects
MH  - Blotting, Western
MH  - Densitometry
MH  - Disease Models, Animal
MH  - Dogs
MH  - Electrocardiography
MH  - Electrophoresis, Gel, Two-Dimensional
MH  - Heart Rate/drug effects
MH  - Matrix Metalloproteinase 2/metabolism
MH  - Matrix Metalloproteinase 9/*metabolism
MH  - Myocardial Infarction/*drug therapy/physiopathology
MH  - Myocardial Reperfusion
MH  - Random Allocation
MH  - Tetrazoles/pharmacology/therapeutic use
MH  - Tissue Inhibitor of Metalloproteinase-3/*metabolism
MH  - Treatment Outcome
MH  - Valine/*analogs & derivatives/pharmacology/therapeutic use
MH  - Valsartan
MH  - Ventricular Dysfunction, Left/drug therapy/*metabolism
EDAT- 2004/10/08 09:00
MHDA- 2005/06/24 09:00
CRDT- 2004/10/08 09:00
PHST- 2004/10/08 09:00 [pubmed]
PHST- 2005/06/24 09:00 [medline]
PHST- 2004/10/08 09:00 [entrez]
AID - S1071916404000351 [pii]
AID - 10.1016/j.cardfail.2004.01.012 [doi]
PST - ppublish
SO  - J Card Fail. 2004 Oct;10(5):442-9. doi: 10.1016/j.cardfail.2004.01.012.