Gene expression profiling of oxidative stress on atrial fibrillation in humans

다국어 초록 (Multilingual Abstract)

Atrial Fibrillation (AF) is thought to be caused by oxidative stress. Oxidative stress at the cellular level results from many factors, including expo- sure to alcohol, medications, cold, toxins or radia- tion. In this study we have investigated the gene transcriptional profiles on the human myocardial tissues from AF and oxidative stress. Right atrial appendages were obtained from AF patients (n = 26) undergoing the Maze procedure and from control patients (n = 26) who were in normal sinus rhythm and undergoing coronary artery bypass graft operation. To examine the effects of oxida- tive stress on AF, radioactive complementary DNA (cDNA) microarrays were used to evaluate changes in the expression of known 1,152 genes in a total.
This technology promises to monitor thousands of genes simultaneously so that we could have a better picture of the interactions between AF and oxidative stress. Total RNAs prepared from the retrieved tissues were used to synthesize 33 P-la- beled cDNAs by reverse transcription and hybri- dized to cDNA microarrays. Gene expression pro- files showed 30 genes were up and 25 genes- down regulated in AF patients when comparing with control patients. Moreover, comparison rank analysis revealed that the expression of five genes related to reactive oxygen species (ROS), including flavin containing monooxygenase 1, monoamine oxidase B, ubiquitin specific protease 8, tyrosi- nase-related protein 1, and tyrosine 3-monooxy- genase, increased by more than 2.0 of Z-ratio and two genes related to antioxidant, including gluta- thione peroxidase 1, and heme oxygenase 2, de- creased by less than -2.0 of Z-ratio in at least one of the five time multiplicated experiments. Appa- rently, a balanced regulation of pro-oxidation and anti-oxidation can be shifted toward pro-oxidation and can result in serious damage like human AF.
Western blotting analysis confirmed the up-regula- tion of tyrosinase-related protein 1 and tyrosine 3-monooxygenase and the down-regulation of heme oxygenase 2. These results suggested that gene expression pattern of myocardial tissues in AF patients can be associated with oxidative stress which results in a significant increase in ROS.
Thus, the cDNA microarray technique was useful for investigation of the transcription profiles in AF so that the intracellular mechanism of oxidative stress plays a pivotal role in the pathologic progression of AF and offers novel insight into potential treatment of antioxidants.