Korean J Pediatr.  2005 Feb;48(2):197-203.

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

• Hong YM

Abstract

PURPOSE
Changes in metalloproteinases(MMP) activity have been demonstrated in several disease states, including rheumatoid arthritis and tumor metastasis. More importantly, increased myocardial MMP activity 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)-alpha 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-alpha 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-alpha(r=0.41, P<0.05). There was no gene expression of MMP, IL-6 or TNF-alpha 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-alpha 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.

Keyword

Gene; Metalloproteinases; Cytokines; Adriamycin

MeSH Terms

Animals
Arthritis, Rheumatoid
Cardiomyopathies*
Cardiomyopathy, Dilated
Clone Cells
Cytokines*
Diagnostic Tests, Routine
DNA, Complementary
Doxorubicin
Extracellular Matrix
Gene Expression*
Heart
Humans
Injections, Intraperitoneal
Interleukin-6
Male
Mass Screening
Metalloproteases*
Necrosis
Neoplasm Metastasis
Oligonucleotide Array Sequence Analysis
Rats
Rats, Sprague-Dawley
Reverse Transcription
RNA
Tumor Necrosis Factor-alpha
Cytokines
DNA, Complementary
Doxorubicin
Interleukin-6
Metalloproteases
RNA
Tumor Necrosis Factor-alpha