Human Molecular Genetics Advance Access published online on May 5, 2004
Human Molecular Genetics, doi:10.1093/hmg/ddh147
© 2004 by Oxford University Press
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1 Department of Clinical Pharmacology, Benjamin Franklin Medical Center, Free University of Berlin, Berlin 12200; Center for Molecular Genetics, Lerner Research Institute, ND4-67, The Cleveland Clinic Foundation. 9500 Euclid Avenue, Cleveland, OH 44195, USA
* To whom correspondence should be addressed. E-mail: tianx{at}ccf.org.
Increased cardiac angiotensin converting enzyme-1 (ACE1) is found in the individuals who carry a deletion in the intron 16 of ACE1 gene or who suffer from cardiac disorders, such as hypertrophy. However, whether a single increase in ACE1 expression leads to spontaneous cardiac defects remains unknown. To determine if the increased cardiac ACE1 actively plays a role or is merely the consequence of pathological changes in the process of cardiac hypertrophy, we generated a transgenic rat model with selective over-expression of human ACE1 in the cardiac ventricles. The left ventricular ACE1 activity is elevated about 50-fold in transgenic rats. Angiotensin-1 perfusion of isolated hearts demonstrated a significant decrease in coronary artery flow compared with non-transgenic littermates, suggesting that the transgenic ACE1 is functional. Neither cardiac hypertrophy nor other morphological abnormalities were observed in transgenic rats under standard living conditions. It was found, however, after induction of hypertension by suprarenal aortic banding, that the degree of cardiac hypertrophy in transgenic rats was significantly higher than that of banded control rats. The expressions of both ANF and collagen III, molecular markers of cardiac hypertrophy, were also increased in banded transgenic rats compared with banded control. Our results suggest that increased cardiac ACE1 does not trigger but augments cardiac hypertrophy.
Article
Over-expression of angiotensin converting enzyme-1 augments cardiac hypertrophy in transgenic rats
2 Department of Clinical Pharmacology, Benjamin Franklin Medical Center, Free University of Berlin, Berlin 12200
3 Department of Internal Medicine, University of Lübeck, Lübeck D-23538
4 Hypertension Research, Max-Delbrück Center (MDC) for Molecular Medicine, Berlin 13092
5 Department of Pharmacology, University of Kiel, Kiel 24105, Germany
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