Journal Article

Over-expression of angiotensin converting enzyme-1 augments cardiac hypertrophy in transgenic rats

Xiao-Li Tian, Yigal Martin Pinto, Olivier Costerousse, Wolfgang M. Franz, Andrea Lippoldt, Sigrid Hoffmann, Thomas Unger and Martin Paul

in Human Molecular Genetics

Volume 13, issue 14, pages 1441-1450
Published in print July 2004 | ISSN: 0964-6906
Published online May 2004 | e-ISSN: 1460-2083 | DOI:
Over-expression of angiotensin converting enzyme-1 augments cardiac hypertrophy in transgenic rats

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Increased cardiac angiotensin converting enzyme-1 (ACE1) is found in individuals who carry a deletion in intron 16 of ACE1 gene or in individuals 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.

Journal Article.  6100 words.  Illustrated.

Subjects: Genetics and Genomics

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