title: Aerobic capacity-dependent differences in cardiac gene expression.
abstract: Aerobic capacity is a strong predictor of cardiovascular mortality. To determine the relationship between inborn aerobic capacity and cardiac gene expression we examined genome-wide gene expression in hearts of rats artificially selected for high and low running capacity (HCR and LCR, respectively) over 16 generations. The artificial selection of LCR caused accumulation of risk factors of cardiovascular disease similar to the metabolic syndrome seen in human, whereas HCR had markedly better cardiac function. We also studied alterations in gene expression in response to exercise training in these animals. Left ventricle gene expression of both sedentary and exercise-trained HCR and LCR was characterized by microarray and gene ontology analysis. Out of 28,000 screened genes, 1,540 were differentially expressed between sedentary HCR and LCR. Only one gene was found differentially expressed by exercise training, but this gene had unknown name and function. Sedentary HCR expressed higher amounts of genes involved in lipid metabolism, whereas sedentary LCR expressed higher amounts of the genes involved in glucose metabolism. This suggests a switch in cardiac energy substrate utilization from normal mitochondrial fatty acid beta-oxidation in HCR to carbohydrate metabolism in LCR, an event that often occurs in diseased hearts. LCR were also associated with pathological growth signaling and cellular stress. Hypoxic conditions seemed to be a common source for several of these observations, triggering hypoxia-induced alterations of transcription. In conclusion, inborn high vs. low aerobic capacity was associated with differences in cardiac energy substrate, growth signaling, and cellular stress.
authors.affiliation: Department of Circulation, Norwegian University of Science and Technology, Trondheim, Norway.
authors.forename: Anja
authors.initials: A
authors.lastname: Bye
authors.forename: Mette
authors.initials: M
authors.lastname: Langaas
authors.forename: Morten A
authors.initials: MA
authors.lastname: Høydal
authors.forename: Ole Johan
authors.initials: OJ
authors.lastname: Kemi
authors.forename: Garrett
authors.initials: G
authors.lastname: Heinrich
authors.forename: Lauren G
authors.initials: LG
authors.lastname: Koch
authors.forename: Steven L
authors.initials: SL
authors.lastname: Britton
authors.forename: Sonia M
authors.initials: SM
authors.lastname: Najjar
authors.forename: Øyvind
authors.initials: Ø
authors.lastname: Ellingsen
authors.forename: Ulrik
authors.initials: U
authors.lastname: Wisløff
mesh_terms: D000818:Animals; D016000:Cluster Analysis; D017079:Exercise Tolerance / Q000235:genetics*; D005260:Female; D020869:Gene Expression Profiling; D006352:Heart Ventricles / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D010805:Physical Conditioning, Animal / Q000502:physiology*; D051381:Rats; D012420:Running / Q000502:physiology; D015398:Signal Transduction / Q000235:genetics; D014797:Vital Capacity / Q000235:genetics*