Genetically determined angiotensin converting ... - The FASEB Journal

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Oliver Smithies, François Alhenc-Gelas,*,†,§ and Christine Richer*,§,¶,1. *INSERM U872, Centre de Recherche des Cordeliers, Paris, France; †Université Paris ...

The FASEB Journal • Research Communication

Genetically determined angiotensin converting enzyme level and myocardial tolerance to ischemia Erij Messadi,* Marie-Pascale Vincent,* Violaine Griol-Charhbili,* Chantal Mandet,*,† Juliana Colucci,* John H. Krege,‡ Patrick Bruneval,*,†,§ Nadine Bouby,* Oliver Smithies,储 Franc¸ois Alhenc-Gelas,*,†,§ and Christine Richer*,§,¶,1 *

INSERM U872, Centre de Recherche des Cordeliers, Paris, France; †Universite´ Paris Descartes, Paris, France; ‡Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana, USA; § Assistance Publique, Hoˆpitaux de Paris, Paris, France; 储Department of Pathology, University of North Carolina, Chapel Hill, North Carolina, USA; and ¶Universite´ Paris-Sud, Le Kremlin-Biceˆtre, France Angiotensin I-converting enzyme (ACE; kininase II) levels in humans are genetically determined. ACE levels have been linked to risk of myocardial infarction, but the association has been inconsistent, and the causality underlying it remains undocumented. We tested the hypothesis that genetic variation in ACE levels influences myocardial tolerance to ischemia. We studied ischemia-reperfusion injury in mice bearing 1 (ACE1c), 2 (ACE2c, wild type), or 3 (ACE3c) functional copies of the ACE gene and displaying an ACE level range similar to humans. Infarct size in ACE1c was 29% lower than in ACE2c (P

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