Matrix metalloproteinase inhibition improves cardiac dysfunction and remodeling in 2-kidney, 1-clip hypertension.

Abstract

BACKGROUND:

Enhanced cardiac matrix metalloproteinase activity (MMPs) has been associated with ventricular remodeling and cardiac dysfunction. It is unknown whether MMPs contribute to systolic/diastolic dysfunction and compensatory remodeling in 2-kidney, 1-clip (2K1C) hypertensive rats. To test this hypothesis, we used 2K1C rats after 2 weeks of surgery treated or not with a nonspecific inhibitor of MMPs (doxycycline).

METHODS AND RESULTS:

We found that blood pressure and +/- dP/dt increased in 2K1C rats compared with sham groups, and these parameters were attenuated by doxycycline treatment (P < .05). Doxycycline also reversed cardiac hypertrophy observed in 2K1C rats (P < .05). Hypertensive rats showed increased MMP-2 levels in zymograms and in the tissue by immunofluorescence (P < .05) compared with sham groups. Increased total gelatinolytic activity was observed in untreated 2K1C rats when compared with sham groups (P < .05). Doxycycline decreased total gelatinolytic activity in 2K1C rats to control levels (P < .05).

CONCLUSION:

An imbalance in gelatinolytic activity, with increased MMP-2 levels and activity underlies the development of morphological and functional alterations found in the compensatory hypertrophy observed in 2K1C hearts. Because function and structure were restored by doxycycline, the inhibition of MMPs or their modulation may provide beneficial effects for therapeutic intervention in cardiac hypertrophy.

• Authors: Elen Rizzi, Michele M Castro, Cibele M Prado, Carlos A Silva, Rubens Fazan Jr, Marcos A Rossi, Jose E Tanus-Santos, Raquel Fernanda Gerlach
• Journal: Journal of cardiac failure (J Card Fail) Vol. 16 Issue 7 Pg. 599-608 (Jul 2010) ISSN: 1532-8414 [Electronic] United States
• PMID: 20610236 (Publication Type: Comparative Study, Journal Article)
• Copyright: Copyright 2010 Elsevier Inc. All rights reserved.

Chemical References

• Enzyme Inhibitors
• Matrix Metalloproteinase Inhibitors
• Matrix Metalloproteinase 2
• Mmp2 protein, rat
• Doxycycline

Topics

• Animals
• Cardiomegaly (drug therapy, enzymology, physiopathology)
• Doxycycline (pharmacology, therapeutic use)
• Enzyme Inhibitors (pharmacology, therapeutic use)
• Hypertension, Renovascular (drug therapy, enzymology, physiopathology)
• Male
• Matrix Metalloproteinase 2 (physiology)
• Matrix Metalloproteinase Inhibitors
• Rats
• Rats, Wistar
• Surgical Instruments
• Ventricular Remodeling (physiology)