Microarray analysis of gene expression profiles of cardiac myocytes and fibroblasts after mechanical stress, ionising or ultraviolet radiation.
BACKGROUND
During excessive pressure or volume overload, cardiac cells are subjected to increased mechanical stress (MS). We set out to investigate how the stress response of cardiac cells to MS can be compared to genotoxic stresses induced by DNA damaging agents. We chose for this purpose to use ionising radiation (IR), which during mediastinal radiotherapy can result in cardiac tissue remodelling and diminished heart function, and ultraviolet radiation (UV) that in contrast to IR induces high concentrations of DNA replication- and transcription-blocking lesions.


RESULTS
Cultures enriched for neonatal rat cardiac myocytes (CM) or fibroblasts were subjected to any one of the three stressors. Affymetrix microarrays, analysed with Linear Modelling on Probe Level, were used to determine gene expression patterns at 24 hours after (the start of) treatment. The numbers of differentially expressed genes after UV were considerably higher than after IR or MS. Remarkably, after all three stressors the predominant gene expression response in CM-enriched fractions was up-regulation, while in fibroblasts genes were more frequently down-regulated. To investigate the activation or repression of specific cellular pathways, genes present on the array were assigned to 25 groups, based on their biological function. As an example, in the group of cholesterol biosynthesis a significant proportion of genes was up-regulated in CM-enriched fractions after MS, but down-regulated after IR or UV.


CONCLUSIONS
Gene expression responses after the types of cellular stress investigated (MS, IR or UV) have a high stressor and cell type specificity.
Boerma
Marjan
M
Department of Toxicogenetics, Leiden University Medical Center, Wassenaarseweg 72, 2333 AL Leiden, The Netherlands. mboerma@uams.edu
van der Wees
Caroline G C
CG
Vrieling
Harry
H
Svensson
J Peter
JP
Wondergem
Jan
J
van der Laarse
Arnoud
A
Mullenders
Leon H F
LH
van Zeeland
Albert A
AA
D000818:Animals; D002478:Cells, Cultured; D004247:DNA / Q000378:metabolism; D004249:DNA Damage; D004260:DNA Repair; D018076:DNA, Complementary / Q000378:metabolism; D015536:Down-Regulation; D005347:Fibroblasts / Q000378:metabolism* / Q000528:radiation effects; D015870:Gene Expression; D020869:Gene Expression Profiling / Q000379:methods*; D005786:Gene Expression Regulation; D005821:Genetic Techniques; D032383:Myocytes, Cardiac / Q000378:metabolism* / Q000528:radiation effects; D009693:Nucleic Acid Hybridization; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D016133:Polymerase Chain Reaction; D011312:Pressure; D011839:Radiation, Ionizing; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013314:Stress, Mechanical; D019063:Tenascin / Q000378:metabolism; D014158:Transcription, Genetic; D014466:Ultraviolet Rays; D015854:Up-Regulation; D014965:X-Rays
D018076:DNA, Complementary; D019063:Tenascin; D004247:DNA