All issues > Volume 48(2); 2005

Original Article

Korean J Pediatr. 2005;48(2):197-203. Published online February 15, 2005.

Gene Expression of Metalloproteinases, Tissue Inhibitors of Metalloproteinases and Cytokines in Adriamycin-induced Cardiomyopathy

Young Mi YM Hong¹

¹Department of Pediatrics, College of Medicine, Ewha Womans University, Seoul, Korea

Correspondence Young Mi YM Hong ,Email: hongym@chollian.net

Abstract

ity has been reported to occur in both clinical and experimental forms of dilated cardiomyopathy. There was no report about MMP in adriamycin(ADR)-induced cardiomyopathy. The purpose of this study was to investigate gene expression of MMP and tissue inhibitor of metalloproteinases(TIMP) in ADR-induced cardiomyopathy and clarify the relationship between MMP and cytokines.
Methods
: Male Sprague-Dawley rats were divided into two groups. The first group was control. The second group was given intraperitoneal injections of ADR(5 mg/kg) twice a week over two weeks. Serum concentrations of MMP, TIMP, interleukin(IL)-6 and tumor necrosis factor(TNF)-α were measured. RNA extraction was performed from frozen rat hearts. Reverse transcription polymerase chain reaction(RT-PCR) was employed. cDNA Microarray analysis was performed by using a set of 5,184 sequence-verified rat cDNA clones.
Results
: Serum MMP and TIMP levels were not significantly different between the two groups. IL-6 was 36.8±2.8 pg/mL and TNF-α 2.2±2.7 pg/mL in the ADR group. They were significantly higher than in the control group. Serum MMP correlated significantly with TNF-α(r=0.41, P<0.05). There was no gene expression of MMP, IL-6 or TNF-α in the hearts of both groups. Gene expression of TIMP was significantly depressed in the hearts of the ADR group.
Conclusion
: These results suggested a potential role for TNF-α in the regulation of extracellular matrix remodeling in ADR induced cardiomyopathy. Rapid screening of multiple decreased gene expression by DNA chip may be a useful diagnostic test to detect early cardiac injury before developing ADR induced cardiomyopathy.

Keywords :Gene, Metalloproteinases , Cytokines , Adriamycin