Enhanced gene expression of myocardial matrix metalloproteinases 2 and 9 after acute treatment with doxorubicin in mice.

We investigated the expression of the genes for matrix metalloproteinases (MMP)-2 and MMP-9 in the ventricle for 1, 2 and 4 days after acute treatment with doxorubicin (DOX) to induce cardiomyopathy in mice, at a single dose of 25 mg kg(-1). Ventricle weights, ventricle weight-to-tail length ratios, and left ventricular systolic and diastolic internal dimensions all decreased time-dependently. Histology showed increased vacuolisation of cardiomyocytes in the DOX-treated mice on day 4 compared with controls. Northern blot hybridisation revealed that MMP-2 and MMP-9 gene transcripts increased in the ventricle of DOX-treated mice on day 2. MMP-2 mRNA approximately doubled in the DOX-treated mice on days 1 and 2, measured using quantitative real-time reverse transcription polymerase chain reaction. By contrast, MMP-9 mRNA expression did not differ in either group on day 1, whereas it increased significantly to 2.9-fold and 2.1-fold in the DOX-treated mice on days 2 and 4, respectively. Consequently, MMP-2 and MMP-9 gene expressions are induced in the ventricle after treatment with DOX, indicating that they might play an important role in the development of DOX-induced cardiotoxicity.