Project description:The molecular mechanism underlying cardiac remodeling following exercise have been incompletely understood. Until now, most studies have been performed in rodents. We studied cardiac remodeling in the physiologically more relevant animal model, the swine. Microarray analysis was performed on animals that underwent either and exercise protocol or remained sedentary. RNA was isolated from tissue samples from the endocardial layer of the free wall of the left ventricle. RNA was isolated from 8 exercise-trained and 8 sedentary animals 4-5 weeks after start of the protocol. Each group contained 4 males and 4 females. Animals used for the study were 2-3 months old Yorkshire x Landrace swine. Only neutered males entered the study.
Project description:Aerobic capacity is a strong predictor of cardiovascular mortality. To determine the relationship between 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. HCR were born with an athletic phenotype, whereas LCR exhibited features of the metabolic syndrome. Left ventricle gene expression of both sedentary and exercise trained HCR and LCR was characterized by microarray- and gene ontology analysis. Western immunoblots and immunohistochemistry were used to validate the results at protein level. Out of 28.0000 screened genes, 1540 were differentially expressed between HCR and LCR. HCR expressed higher amounts of genes involved in lipid metabolism, whereas LCR expressed higher amounts of the genes involved in glucose metabolism and transport. By simply selecting for running capacity, we created a difference in cardiac energy substrate utilisation from normal mitochondrial fatty acid betaoxidation in HCR to carbohydrate metabolism in LCR. This event often occurs in diseased hearts. Differential expression of genes involved in cardiomyocyte growth was also found. LCR rats were associated with fetal gene expression, indicating the presence of pathological remodelling signaling. In addition, different expression of genes associated with cardiac contractility and cellular stress were detected. Also, hypoxia triggered transcription seemed to be involved in several of the functional differences between HCR and LCR. In conclusion, high- versus low aerobic capacity was associated with differences in genes regulating cardiac energy substrate, growth signalling, contractility and cellular stress. Keywords: metabolic syndrome analysis