title: Matrix metalloprotease activity is enhanced in the compensated but not in the decompensated phase of pressure overload hypertrophy.
abstract: 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.
authors.affiliation: Clinica Medica II, Fondazione IRCCS San Matteo, University of Pavia, Pavia, Italy.
authors.forename: Rossana
authors.initials: R
authors.lastname: Tozzi
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Palladini
authors.forename: Silvia
authors.initials: S
authors.lastname: Fallarini
authors.forename: Rosanna
authors.initials: R
authors.lastname: Nano
authors.forename: Chiara
authors.initials: C
authors.lastname: Gatti
authors.forename: Cristina
authors.initials: C
authors.lastname: Presotto
authors.forename: Antonio
authors.initials: A
authors.lastname: Schiavone
authors.forename: Rosella
authors.initials: R
authors.lastname: Micheletti
authors.forename: Patrizia
authors.initials: P
authors.lastname: Ferrari
authors.forename: Roberto
authors.initials: R
authors.lastname: Fogari
authors.forename: Stefano
authors.initials: S
authors.lastname: Perlini
mesh_terms: 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
chemical_list: D019714:Tissue Inhibitor of Metalloproteinases; D003094:Collagen; D020782:Matrix Metalloproteinases