Comparison of gene expression profiling in pressure and volume overload-induced myocardial hypertrophies in rats.
Gene expression profiling has been conducted in rat hearts subjected to pressure overload (PO). However, pressure and volume overload produce morphologically and functionally distinct forms of cardiac hypertrophy. Surprisingly, gene expression profiling has not been reported for in an animal model of volume overload (VO). We therefore compared the gene expression profiles in the hypertrophied myocardium of rats subjected to PO and VO using DNA chip technology (Affymetrix U34A). Constriction of the abdominal aorta and abdominal aortocaval shunting were used to induce PO and VO, respectively. The gene expression profiles of the left ventricle (LV) 4 weeks after the procedure were analyzed by DNA chips. There were comparable increases in the left ventricular weight/body weight ratio in rats subjected to PO and VO. Echocardiography revealed concentric hypertrophy in the PO animals, but eccentric hypertrophy in the rats subjected to VO. The expressions of many genes were altered in VO, PO, or both. Among the genes that were upregulated in both forms of hypertrophy, greatly increased expressions of B-type natriuretic peptide, lysyl oxidase-like protein 1 and metallothionein-1 (MT) were confirmed by real-time reverse transcription-polymerase chain reaction (RT-PCR). Because free radicals are increased in the hypertrophied heart and may contribute to apoptosis, we examined the role of MT, a free radical scavenger, in apoptosis. The over-expression of MT in H9c2 cells inhibited norepinephrine-induced apoptosis, suggesting that MT may act as an anti-apoptotic molecule in cardiac hypertrophy. In conclusion, we found that many genes were regulated in VO, PO, or both. In addition, a novel role of MT in the hypertrophied myocardium was suggested.
Miyazaki
Hiroshi
H
Department of Medicine, Division of Cardio-Vascular Medicine, Kurume University School of Medicine, Kurume, Japan.
Oka
Naoki
N
Koga
Akimasa
A
Ohmura
Haruya
H
Ueda
Tamenobu
T
Imaizumi
Tsutomu
T
D000818:Animals; D002306:Cardiac Volume; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D017379:Hypertrophy, Left Ventricular / Q000235:genetics*; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D011312:Pressure; D051381:Rats; D017208:Rats, Wistar