title: Transcriptional Changes Associated with Long-Term Left Ventricle Volume Overload in Rats: Impact on Enzymes Related to Myocardial Energy Metabolism.
abstract: Patients with left ventricle (LV) volume overload (VO) remain in a compensated state for many years although severe dilation is present. The myocardial capacity to fulfill its energetic demand may delay decompensation. We performed a gene expression profile, a model of chronic VO in rat LV with severe aortic valve regurgitation (AR) for 9 months, and focused on the study of genes associated with myocardial energetics. Methods. LV gene expression profile was performed in rats after 9 months of AR and compared to sham-operated controls. LV glucose and fatty acid (FA) uptake was also evaluated in vivo by positron emission tomography in 8-week AR rats treated or not with fenofibrate, an activator of FA oxidation (FAO). Results. Many LV genes associated with mitochondrial function and metabolism were downregulated in AR rats. FA β-oxidation capacity was significantly impaired as early as two weeks after AR. Treatment with fenofibrate, a PPARα agonist, normalized both FA and glucose uptake while reducing LV dilation caused by AR. Conclusion. Myocardial energy substrate preference is affected early in the evolution of LV-VO cardiomyopathy. Maintaining a relatively normal FA utilization in the myocardium could translate into less glucose uptake and possibly lesser LV remodeling.
authors.affiliation: Groupe de Recherche sur les Valvulopathies, Centre de Recherche, Institut Universitaire de Cardiologie et de Pneumologie de Québec, Université Laval, Quebec City, QC, Canada G1V 4G5.
authors.forename: Elise
authors.initials: E
authors.lastname: Roussel
authors.affiliation: Groupe de Recherche sur les Valvulopathies, Centre de Recherche, Institut Universitaire de Cardiologie et de Pneumologie de Québec, Université Laval, Quebec City, QC, Canada G1V 4G5.
authors.forename: Marie-Claude
authors.initials: MC
authors.lastname: Drolet
authors.affiliation: Groupe de Recherche sur les Valvulopathies, Centre de Recherche, Institut Universitaire de Cardiologie et de Pneumologie de Québec, Université Laval, Quebec City, QC, Canada G1V 4G5.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Walsh-Wilkinson
authors.affiliation: Groupe de Recherche sur les Valvulopathies, Centre de Recherche, Institut Universitaire de Cardiologie et de Pneumologie de Québec, Université Laval, Quebec City, QC, Canada G1V 4G5.
authors.forename: Wahiba
authors.initials: W
authors.lastname: Dhahri
authors.affiliation: Groupe de Recherche sur les Valvulopathies, Centre de Recherche, Institut Universitaire de Cardiologie et de Pneumologie de Québec, Université Laval, Quebec City, QC, Canada G1V 4G5.
authors.forename: Dominic
authors.initials: D
authors.lastname: Lachance
authors.affiliation: Sherbrooke Molecular Imaging Center, Research Center of Centre Hospitalier Universitaire de Sherbrooke (CRCHUS), Université de Sherbrooke, Sherbrooke, QC, Canada J1H 5N4.
authors.forename: Suzanne
authors.initials: S
authors.lastname: Gascon
authors.affiliation: Sherbrooke Molecular Imaging Center, Research Center of Centre Hospitalier Universitaire de Sherbrooke (CRCHUS), Université de Sherbrooke, Sherbrooke, QC, Canada J1H 5N4.
authors.forename: Otman
authors.initials: O
authors.lastname: Sarrhini
authors.affiliation: Sherbrooke Molecular Imaging Center, Research Center of Centre Hospitalier Universitaire de Sherbrooke (CRCHUS), Université de Sherbrooke, Sherbrooke, QC, Canada J1H 5N4.
authors.forename: Jacques A
authors.initials: JA
authors.lastname: Rousseau
authors.affiliation: Sherbrooke Molecular Imaging Center, Research Center of Centre Hospitalier Universitaire de Sherbrooke (CRCHUS), Université de Sherbrooke, Sherbrooke, QC, Canada J1H 5N4.
authors.forename: Roger
authors.initials: R
authors.lastname: Lecomte
authors.affiliation: Groupe de Recherche sur les Valvulopathies, Centre de Recherche, Institut Universitaire de Cardiologie et de Pneumologie de Québec, Université Laval, Quebec City, QC, Canada G1V 4G5.
authors.forename: Jacques
authors.initials: J
authors.lastname: Couet
authors.affiliation: Groupe de Recherche sur les Valvulopathies, Centre de Recherche, Institut Universitaire de Cardiologie et de Pneumologie de Québec, Université Laval, Quebec City, QC, Canada G1V 4G5.
authors.forename: Marie
authors.initials: M
authors.lastname: Arsenault
mesh_terms: D000818:Animals; D001022:Aortic Valve Insufficiency / Q000188:drug therapy / Q000235:genetics* / Q000503:physiopathology; D002306:Cardiac Volume / Q000235:genetics; D004195:Disease Models, Animal; D004734:Energy Metabolism / Q000235:genetics*; D011345:Fenofibrate / Q000008:administration & dosage; D006333:Heart Failure / Q000188:drug therapy / Q000235:genetics* / Q000503:physiopathology; D006352:Heart Ventricles / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D006801:Humans; D017379:Hypertrophy, Left Ventricular / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D008929:Mitochondria, Heart / Q000235:genetics; D010084:Oxidation-Reduction; D047493:PPAR alpha / Q000235:genetics; D051381:Rats; D059467:Transcriptome; D016277:Ventricular Function, Left / Q000187:drug effects / Q000235:genetics
chemical_list: D047493:PPAR alpha; D011345:Fenofibrate