Journal article

Animal model - Mice with cardiac-restricted angiotensin-converting enzyme (ACE) have atrial enlargement, cardiac arrhythmia, and sudden death

HD Xiao, S Fuchs, DJ Campbell, W Lewis, SC Dudley, VS Kasi, BD Hoit, G Keshelava, H Zhao, MR Capecchi, KE Bernstein

American Journal of Pathology | ELSEVIER SCIENCE INC | Published : 2004


To investigate the local effects of angiotensin II on the heart, we created a mouse model with 100-fold normal cardiac angiotensin-converting enzyme (ACE), but no ACE expression in kidney or vascular endothelium. This was achieved by placing the endogenous ACE gene under the control of the alpha-myosin heavy chain promoter using targeted homologous recombination. These mice, called ACE 8/8, have cardiac angiotensin II levels that are 4.3-fold those of wild-type mice. Despite near normal blood pressure and a normal renal function, ACE 8/8 mice have a high incidence of sudden death. Both histological analysis and in vivo catheterization of the heart showed normal ventricular size and function...

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