Matrix metalloprotease activity is enhanced in the compensated but not in the decompensated phase of pressure overload hypertrophy.
BACKGROUND
During the transition of pressure overload hypertrophy (POH) to heart failure (HF) there is intense interstitial cardiac remodeling, characterized by a complex balance between collagen deposition and degradation by matrix metalloproteases (MMPs). This study was aimed at investigating the process of cardiac remodeling during the different phases of the transition of POH to HF.


METHODS
Guinea pigs underwent thoracic descending aortic banding or sham operation. Twelve weeks after surgery, left-ventricular (LV) end-diastolic internal dimension and ventricular systolic pressure were measured by combined M-mode echocardiography and micromanometer cathetherization. The MMP activity, tissue-specific MMP inhibitors (TIMPs), and collagen fraction were evaluated in LV tissue samples by zymography, ELISA, and computer-aided analysis, respectively.


RESULTS
Banded animals were divided by lung weight values into either compensated left-ventricular hypertrophy (LVH) or HF groups, as compared with sham-operated controls. All HF animals exhibited a restrictive pattern of Doppler transmitral inflow, indicative of diastolic dysfunction, and developed lung congestion. Compensated LVH was associated with increased MMP-2 activity, which was blunted after transition to HF, at a time when TIMP-2 levels and collagen deposition were increased.


CONCLUSIONS
The cardiac remodeling process that accompanies the development of POH is a phase-dependent process associated with progressive deterioration of cardiac function.
Tozzi
Rossana
R
Clinica Medica II, Fondazione IRCCS San Matteo, University of Pavia, Pavia, Italy.
Palladini
Giuseppina
G
Fallarini
Silvia
S
Nano
Rosanna
R
Gatti
Chiara
C
Presotto
Cristina
C
Schiavone
Antonio
A
Micheletti
Rosella
R
Ferrari
Patrizia
P
Fogari
Roberto
R
Perlini
Stefano
S
D000818:Animals; D001794:Blood Pressure / Q000502:physiology; D002303:Cardiac Output, Low / Q000201:enzymology / Q000473:pathology / Q000503:physiopathology; D002311:Cardiomyopathy, Dilated / Q000201:enzymology* / Q000473:pathology / Q000503:physiopathology; D003094:Collagen / Q000378:metabolism; D018450:Disease Progression; D004452:Echocardiography; D006168:Guinea Pigs; D006352:Heart Ventricles / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D017379:Hypertrophy, Left Ventricular / Q000201:enzymology* / Q000473:pathology / Q000503:physiopathology; D008297:Male; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D019714:Tissue Inhibitor of Metalloproteinases / Q000378:metabolism; D018487:Ventricular Dysfunction, Left / Q000503:physiopathology; D020257:Ventricular Remodeling / Q000502:physiology
D019714:Tissue Inhibitor of Metalloproteinases; D003094:Collagen; D020782:Matrix Metalloproteinases