HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Free Full Text (PDF) Free All Versions of this Article: 101/2/385    most recent 01486.2005v1 Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (11) Citing Articles via Google Scholar Google Scholar Articles by Zoll, J. Articles by Geny, B. Search for Related Content PubMed PubMed Citation Articles by Zoll, J. Articles by Geny, B.

ACE inhibition prevents myocardial infarction-induced skeletal muscle mitochondrial dysfunction

¹Service de Physiologie et d'Explorations Fonctionnelles, EA 3072 and ²Laboratoire de Neurobiologie et de Pharmacologie Cardiovasculaire, INSERM U715, Hôpitaux Universitaires de Strasbourg, Faculté de Médecine, Strasbourg; and ³Cardiologie Cellulaire et Moléculaire U769 INSERM, Faculté de Pharmacie, Université Paris-Sud, Châtenay-Malabry, France

Submitted 28 November 2005 ; accepted in final form 31 March 2006

Heart failure is associated with alterations in cardiac and skeletal muscle energy metabolism resulting in a generalized myopathy. We investigated the molecular and cellular effects of angiotensin-converting enzyme inhibition (ACEi) on skeletal muscle metabolism in infarcted animals. Myocardial infarction (MI) was obtained by left descending coronary artery ligation. Sham, MI, and MI-treated rats (perindopril, 2 mg·kg^–1·day^–1 given 7 days after MI) were studied 1 and 4 mo after surgery. Oxygen consumption of white gastrocnemius (Gas) muscle was studied in saponin-permeabilized fibers, using the main substrates of mitochondrial respiration. mRNA expression of nuclear factors (PGC-1, NRF-2, and mtTFA), involved in the transcription of mitochondrial proteins, and of MCIP1, a marker of calcineurin activation, were also determined. Echocardiographic left ventricular fractional shortening was reduced in both MI and perindopril group after 1 and 4 mo, whereas systemic blood pressure was reduced by 16% only in the MI group after 4 mo. The capacity of Gas to oxidize glutamate-malate, glycerol-triphosphate, or pyruvate (–30%, P < 0.01; –32%, P < 0.05; –33%, P < 0.01, respectively), was greatly decreased. Furthermore, PGC-1 (–54%), NRF-2 (–45%), and MCIP1 (–84%) gene expression were significantly downregulated. ACEi improved survival, left ventricular function, and blood pressure. Perindopril protected also totally the Gas mitochondrial function and preserved the mRNAs concentration of the mitochondrial transcriptional factors. Moreover, PGC-1 correlated with Gas oxidative capacity (r = 0.48), mitochondrial cytochrome-c oxidase (r = 0.65), citrate synthase (r = 0.45) activities, and MCIP1 expression (r = 0.44). Thus ACEi totally prevented MI-induced alterations of skeletal muscle mitochondrial function and protein expression, halting the development of this metabolic myopathy.

rehabilitation; mitochondria; angiotensin-converting enzyme inhibition

This article has been cited by other articles:

				E. Habouzit, H. Richard, H. Sanchez, N. Koulmann, B. Serrurier, R. Monnet, R. Ventura-Clapier, and X. Bigard Decreased muscle ACE activity enhances functional response to endurance training in rats, without change in muscle oxidative capacity or contractile phenotype J Appl Physiol, July 1, 2009; 107(1): 346 - 353. [Abstract] [Full Text] [PDF]

				A. Garnier, J. Zoll, D. Fortin, B. N'Guessan, F. Lefebvre, B. Geny, B. Mettauer, V. Veksler, and R. Ventura-Clapier Control by Circulating Factors of Mitochondrial Function and Transcription Cascade in Heart Failure: A Role for Endothelin-1 and Angiotensin II Circ Heart Fail, July 1, 2009; 2(4): 342 - 350. [Abstract] [Full Text] [PDF]

				R. Ventura-Clapier, A. Garnier, and V. Veksler Transcriptional control of mitochondrial biogenesis: the central role of PGC-1{alpha} Cardiovasc Res, July 15, 2008; 79(2): 208 - 217. [Abstract] [Full Text] [PDF]

				A. Mezzani, U. Corra, C. Andriani, A. Giordano, R. Colombo, and P. Giannuzzi Anaerobic and aerobic relative contribution to total energy release during supramaximal effort in patients with left ventricular dysfunction J Appl Physiol, January 1, 2008; 104(1): 97 - 102. [Abstract] [Full Text] [PDF]

				O. Rouyer, J. Zoll, F. Daussin, C. Damge, P. Helms, S. Talha, L. Rasseneur, F. Piquard, and B. Geny Muscle: Effect of angiotensin-converting enzyme inhibition on skeletal muscle oxidative function and exercise capacity in streptozotocin-induced diabetic rats Exp Physiol, November 1, 2007; 92(6): 1047 - 1056. [Abstract] [Full Text] [PDF]

				R. Ventura-Clapier, B. Mettauer, and X. Bigard Beneficial effects of endurance training on cardiac and skeletal muscle energy metabolism in heart failure Cardiovasc Res, January 1, 2007; 73(1): 10 - 18. [Abstract] [Full Text] [PDF]