Abstract
Background The objective of the present study was to investigate whether mTOR is involved in
cardiac fibrosis evident in dilated cardiomyopathy, and whether rapamycin provides
therapeutic potential for cardiac fibrosis.
Methods Forty-five rats were divided into three groups. Fifteen rats in the Adriamycin group
underwent 8 weeks of Adriamycin treatment (2.5 mg/kg, twice per week; i.v.) to induce
cardiac fibrosis and dilated cardiomyopathy. Fifteen rats in the rapamycin group received
rapamycin (2 mg/kg, per day, orally) and i.v. Adriamycin simultaneously for 8 weeks.
Fifteen untreated rats served as controls. Cardiac morphology and function were quantified
using echocardiography. mTOR and p70S6K1 mRNA expression were assessed using reverse
transcription-PCR.
Results Collagen volume fraction (CVF) was significantly elevated in the adriamycin group
(3.36 ± 0.75) compared with controls (1.51 ± 0.31), whereas mTOR and p70S6K mRNA expression
were significantly increased in the adriamycin group (0.68 ± 0.03 and 0.69 ± 0.03)
compared with controls (0.38 ± 0.03 and 0.34 ± 0.02). The Adriamycin group was associated
with cardiac dilation and decreased contractile function. The rapamycin group showed
significantly decreased CVF (1.87 ± 0.45), accompanied with a significant decrease
in mTOR and p70S6K mRNA expression (0.42 ± 0.05 and 0.45 ± 0.04) relative to the Adriamycin
group. In addition, treatment with rapamycin recovered impairments in cardiac morphology
and function.
Conclusion The mTOR/p70S6K pathway plays an important role in adriamycin-induced cardiac fibrosis
resulting from dilated cardiomyopathy. Rapamycin is a potential therapeutic treatment
that can be used to attenuate cardiac fibrosis and improve cardiac function.
Keywords
rapamycin - mTOR/p70S6K - cardiac fibrosis - dilated cardiomyopathy - adriamycin
