Transcriptional profile of genes induced in human atrial myocardium with pressure overload.
BACKGROUND
The molecular response of human myocardium to mechanical stimuli, particularly the difference between pressure or volume overload cardiac hypertrophy, remains incompletely defined.


METHODS
We investigated the transcriptional profile of genes induced in human pressure- or volume-overloaded myocardium with DNA microarray technology. We used right atrial tissue from patients who underwent cardiac surgery. On the basis of pressure data and echocardiographic findings, the patients were divided into three groups: control group (n=3), pressure overload group (mean right atrial pressure of >7 mm Hg, n=3), and volume overload group (moderate or severe tricuspid regurgitation, n=3). Expression profiles of 2139 human genes were investigated with mRNA obtained from the samples.


RESULTS
In the pressure overload group, expression of genes of cyclin-dependent kinase inhibitor 1A (CDKI1A, 11.7+/-3.1-fold vs. control), and mitogen-activated protein kinase phosphatase-1 (MKP-1, 26.2+/-2.1-fold) was significantly increased compared with those in control or volume overload group (P<0.05). The specificity of these gene expressions was confirmed by a quantitative "real-time" polymerase chain reaction (PCR) analysis. In addition, mechanical strain induced CDKI1A and MKP-1 protein expressions in neonatal rat cardiac myocytes in an amplitude-dependent manner. In contrast, transcripts of growth factors did not significantly increase.


CONCLUSIONS
This study demonstrated that gene expressions of CDKI1A and MKP-1, but not growth factors, are induced in chronic pressure-overloaded myocardium. These findings suggest that suppressors of the cell cycle or cell proliferation may play a critical role in the pathophysiology of pressure overload.
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; D000818:Animals; D000831:Animals, Newborn; D020517:Atrial Appendage / Q000378:metabolism*; D018929:Cell Culture Techniques; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D018844:Cyclin-Dependent Kinases / Q000235:genetics / Q000378:metabolism*; D054638:Dual Specificity Phosphatase 1; D005260:Female; D005982:Glutathione Transferase / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D017379:Hypertrophy, Left Ventricular / Q000235:genetics / Q000378:metabolism*; D017874:Immediate-Early Proteins / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D018945:Monocyte Chemoattractant Proteins / Q000235:genetics / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000378:metabolism; D010749:Phosphoprotein Phosphatases / Q000235:genetics / Q000378:metabolism*; D054645:Protein Phosphatase 1; D017027:Protein Tyrosine Phosphatases / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D013314:Stress, Mechanical
D018797:Cell Cycle Proteins; D017874:Immediate-Early Proteins; D018945:Monocyte Chemoattractant Proteins; D012333:RNA, Messenger; C413545:glutathione S-transferase T1; D005982:Glutathione Transferase; D018844:Cyclin-Dependent Kinases; D010749:Phosphoprotein Phosphatases; D054645:Protein Phosphatase 1; C517019:DUSP1 protein, human; D054638:Dual Specificity Phosphatase 1; C517021:Dusp1 protein, rat; D017027:Protein Tyrosine Phosphatases