Gene expression profiling of human atrial myocardium with atrial fibrillation by DNA microarray analysis.
BACKGROUND
Atrial fibrillation (AF) is the most frequently encountered arrhythmia in the clinical setting. However, a comprehensive investigation of the molecular mechanism of AF has not been performed. The aim of this study was to clarify transcriptional profiling of genes modulated in the atrium of AF patients using DNA microarray technology.


METHODS
We obtained 17 fresh cardiac specimens, right atrial appendages, isolated from 10 patients with normal sinus rhythm and seven chronic AF patients who underwent cardiac surgery. Affymetrix GeneChip (Human Genome U95A) investigating 12,000 human genes was used for each specimen. Quantitative analysis of selected genes was performed by the real-time PCR method.


RESULTS
The left atrial diameter in the AF group was greater than that in the sinus rhythm group. We could identify 33 AF-specific genes that were significantly activated (>1.5-fold), compared with the sinus rhythm group, including an ion channel, an antioxidant, an inflammation, three cell growth/cell cycle, three transcription such as nuclear factor-interleukin 6-beta, several cell signaling and several protein genes, and seven expressed sequence tags (ESTs). In contrast, we found 63 sinus rhythm-specific genes, including several cell signaling/communication such as sarcoplasmic reticulum Ca2+-ATPase 2, several cellular respiration and energy production and two antiproliferative or negative regulator of cell growth genes, and 22 ESTs.


CONCLUSIONS
The present study demonstrated that about one hundred genes were modulated in the atria of AF patients. These findings suggest that these genes may play critical roles in the initiation or perpetuation of AF and the pathophysiology of atrial remodeling.
Division of Cardiovascular Medicine, Jichi Medical School, Minamikawachi-Machi, Tochigi 329-0498, Japan.
Ruri
R
Ohki
Keiji
K
Yamamoto
Shuichi
S
Ueno
Hiroyuki
H
Mano
Yoshio
Y
Misawa
Katsuo
K
Fuse
Uichi
U
Ikeda
Kazuyuki
K
Shimada
D000293:Adolescent; D000328:Adult; D000368:Aged; D001281:Atrial Fibrillation / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D051743:CCAAT-Enhancer-Binding Protein-delta; D022762:CCAAT-Enhancer-Binding Proteins / Q000235:genetics / Q000378:metabolism; D000252:Calcium-Transporting ATPases / Q000235:genetics / Q000378:metabolism; D002453:Cell Cycle / Q000235:genetics; D004247:DNA / Q000032:analysis*; D005260:Female; D015870:Gene Expression; D020869:Gene Expression Profiling; D005819:Genetic Markers / Q000235:genetics; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000235:genetics / Q000378:metabolism; D006325:Heart Atria / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D012313:RNA / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D015398:Signal Transduction / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
D022762:CCAAT-Enhancer-Binding Proteins; C497252:CEBPD protein, human; D005819:Genetic Markers; D014157:Transcription Factors; D051743:CCAAT-Enhancer-Binding Protein-delta; D012313:RNA; D004247:DNA; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D000252:Calcium-Transporting ATPases