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.
Kizaki
Keiichiro
K
Department of Veterinary Pharmacology, School of Veterinary Medicine and Animal Sciences, Kitasato University, Towada, Aomori 034-8628, Japan. kizaki@iwate-u.ac.jp
Ito
Ryoichi
R
Okada
Muneyoshi
M
Yoshioka
Kazuki
K
Uchide
Tsuyoshi
T
Temma
Kyosuke
K
Mutoh
Ken-ichiro
K
Uechi
Masami
M
Hara
Yukio
Y
D000818:Animals; D009202:Cardiomyopathies / Q000139:chemically induced / Q000201:enzymology; D004317:Doxorubicin / Q000633:toxicity*; D004452:Echocardiography / Q000379:methods; D015870:Gene Expression / Q000187:drug effects; D006321:Heart / Q000187:drug effects*; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D051379:Mice; D008813:Mice, Inbred ICR; D009206:Myocardium / Q000201:enzymology*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics
D012333:RNA, Messenger; D004317:Doxorubicin; D020782:Matrix Metalloproteinases; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9