PMID- 11955860
OWN - NLM
STAT- MEDLINE
DCOM- 20020510
LR  - 20220227
IS  - 0735-1097 (Print)
IS  - 0735-1097 (Linking)
VI  - 39
IP  - 8
DP  - 2002 Apr 17
TI  - Excessive activation of matrix metalloproteinases coincides with left ventricular 
      remodeling during transition from hypertrophy to heart failure in hypertensive 
      rats.
PG  - 1384-91
AB  - OBJECTIVES: We sought to elucidate how the local activation of matrix 
      metalloproteinases (MMPs) is balanced by that of the endogenous tissue inhibitors 
      of MMP (TIMPs) during left ventricular (LV) remodeling. BACKGROUND: Although it 
      is known that the extracellular matrix (ECM) must be altered during LV 
      remodeling, its local regulation has not been fully elucidated. METHODS: In Dahl 
      salt-sensitive rats with hypertension, in which a stage of concentric, 
      compensated left ventricular hypertrophy (LVH) at 11 weeks is followed by a 
      distinct stage of congestive heart failure (CHF) with LV enlargement and 
      dysfunction at 17 weeks, we determined protein and messenger ribonucleic acid 
      (mRNA) levels of LV myocardial TIMP-2 and -4 and MMP-2, as well as their 
      concomitant activities. RESULTS: No changes were found at the LVH stage. However, 
      during the transition to CHF, TIMP-2 and -4 activities, protein and mRNA levels 
      were all sharply increased. At the same time, the MMP-2 mRNA and protein levels 
      and activities, as determined by gelatin zymography, as well as by an antibody 
      capture assay, showed a substantial increase during the transition to CHF. The 
      net MMP activities were closely related to increases in LV diameter (r = 0.763) 
      and to systolic wall stress (r = 0.858) in vivo. CONCLUSIONS: Both TIMPs and 
      MMP-2 remained inactive during hypertrophy, per se; they were activated during 
      the transition to CHF. At this time, the activation of MMP-2 surpassed that of 
      TIMPs, possibly resulting in ECM breakdown and progression of LV enlargement.
FAU - Iwanaga, Yoshitaka
AU  - Iwanaga Y
AD  - Department of Cardiovascular Medicine, Kyoto University Graduate School of 
      Medicine, Kyoto, Japan.
FAU - Aoyama, Takeshi
AU  - Aoyama T
FAU - Kihara, Yasuki
AU  - Kihara Y
FAU - Onozawa, Yoko
AU  - Onozawa Y
FAU - Yoneda, Takeshi
AU  - Yoneda T
FAU - Sasayama, Shigetake
AU  - Sasayama S
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Am Coll Cardiol
JT  - Journal of the American College of Cardiology
JID - 8301365
RN  - 0 (RNA, Messenger)
RN  - 0 (Tissue Inhibitor of Metalloproteinases)
RN  - EC 3.4.24.- (Matrix Metalloproteinases)
SB  - IM
MH  - Animals
MH  - Blood Pressure/physiology
MH  - Disease Models, Animal
MH  - Disease Progression
MH  - Echocardiography
MH  - Heart/physiopathology
MH  - Heart Failure/*enzymology/*etiology
MH  - Hypertrophy, Left Ventricular/*complications/*enzymology
MH  - Male
MH  - Matrix Metalloproteinases/*metabolism
MH  - Models, Cardiovascular
MH  - Organ Size/physiology
MH  - RNA, Messenger/metabolism
MH  - Rats
MH  - Rats, Inbred Dahl
MH  - Tissue Inhibitor of Metalloproteinases/metabolism
MH  - Ventricular Remodeling/*physiology
EDAT- 2002/04/17 10:00
MHDA- 2002/05/11 10:01
CRDT- 2002/04/17 10:00
PHST- 2002/04/17 10:00 [pubmed]
PHST- 2002/05/11 10:01 [medline]
PHST- 2002/04/17 10:00 [entrez]
AID - S0735109702017564 [pii]
AID - 10.1016/s0735-1097(02)01756-4 [doi]
PST - ppublish
SO  - J Am Coll Cardiol. 2002 Apr 17;39(8):1384-91. doi: 10.1016/s0735-1097(02)01756-4.