Submitted on November 20, 2007
Accepted on December 29, 2007
Aerobic capacity-dependent differences in cardiac gene expression
Anja Bye1, Mette Langaas2, Morten A Hoydal1, Ole Johan Kemi3, Garrett Heinrich4, Lauren G Koch5, Steven L Britton5, Sonia M. Najjar4, Oyvind Ellingsen6, and Ulrik Wisloff7*
1 Dept. of Circulation and Medical Imaging, Norwegian University of Science and Technology, Trondheim, Norway
2 Dept. of Mathematical Sciences, Norwegian University of Science and Technology, Trondheim, Norway
3 Institute of Biomedical and Life Sciences, University of Glasgow, Glasgow, United Kingdom
4 Dept. of Pharmacology, Cardiovascular Biology, and Metabolic Diseases, Medical College of Ohio, Toledo, Ohio, United States
5 Dept. of Physical Medicine and Rehabilitation, University of Michigan, Ann Arbor, Michigan, United States
6 Dept. of Circulation and medical Imaging, Norwegian University of Science and Technology, Trondheim, Norway
7 Circulation and Medical Imaging, Norwegian University of Science and Technology, Olav Kyrres gt. 3, Trondheim, 7489, Norway
* To whom correspondence should be addressed. E-mail: ulrik.wisloff{at}ntnu.no.
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 man, 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 28000 screened genes, 1540 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 utilisation from normal mitochondrial fatty acid 
-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- versus low aerobic capacity was associated with differences in cardiac energy substrate, growth signalling and cellular stress.
