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

Korean Journal of Pediatrics 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 Hong
Department of Pediatrics, College of Medicine, Ewha Womans University, Seoul, Korea
아드리아마이신으로 유도된 심근증에서 Metalloproteinase, Metalloproteinase 조직억제자, Cytokine 유전자 발현에 대한 연구
홍영미
이화대학교 의과대학 동대문병원 소아과
Correspondence: 
Young Mi 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.
Key Words: Gene, Metalloproteinases , Cytokines , Adriamycin


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