Ginsenoside-Rb1 attenuates dilated cardiomyopathy in cTnT(R141W) transgenic mouse.
Familial dilated cardiomyopathy (FDCM) is caused by defective genes and specific medicines are not currently available to treat this. Ginsenoside-Rb1 provides cardioprotection in the experimental models of myocardial ischemia-reperfusion injury. Here we investigate Rb1's effect on DCM in cTnT(R141W) transgenic mouse. The transgene-positive mice aged 2 months were randomized into the model group and Rb1 [70 mg/(kg.day)] group; transgene-negative mice were used as a control. After 4-month treatment, cardiac function was assessed by echocardiography; cardiac tissues were prepared for histology and electron microscopy. Expression levels of molecular markers of cardiac hypertrophy, fibrosis, and intercalated disc proteins were detected by RT-PCR. Rb1 significantly decreased mortality, chamber dilation, and contractile dysfunction in cTnT(R141W) mice. Rb1 attenuated cardiac hypertrophy, interstitial fibrosis, ultrastructural degeneration, and intercalated disc remodeling in DCM hearts. Western blotting showed that Rb1 significantly decreased heparin-binding epidermal growth factor-like growth factor (HB-EGF) expression and signal transduction and activators of transcription 3 (STAT3) activation, which were gradually increased in DCM hearts. Our results showed that Rb1 clearly alleviated cardiac dysfunction and remodeling in the cTnT(R141W) transgenic mouse, indicating its potential utility in the treatment of FDCM.
Zhao
Haiping
H
Key Laboratory of Human Disease Comparative Medicine, Ministry of Health, Institute of Laboratory Animal Science, Chinese Academy of Medical Science & Comparative Medicine Center, Peking Union Medical College, China.
Lv
Dan
D
Zhang
Wei
W
Dong
Wei
W
Feng
Juan
J
Xiang
Zhiguang
Z
Huang
Lan
L
Qin
Chuan
C
Zhang
Lianfeng
L
D000818:Animals; D015153:Blotting, Western; D002311:Cardiomyopathy, Dilated / Q000188:drug therapy* / Q000503:physiopathology; D002316:Cardiotonic Agents / Q000494:pharmacology*; D004452:Echocardiography; D005786:Gene Expression Regulation / Q000187:drug effects; D036145:Ginsenosides / Q000494:pharmacology*; D066257:Heparin-binding EGF-like Growth Factor; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D008854:Microscopy, Electron; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050796:STAT3 Transcription Factor / Q000378:metabolism; D020257:Ventricular Remodeling / Q000187:drug effects
D002316:Cardiotonic Agents; D036145:Ginsenosides; C587883:HBEGF protein, human; C587884:Hbegf protein, mouse; D066257:Heparin-binding EGF-like Growth Factor; D036341:Intercellular Signaling Peptides and Proteins; D050796:STAT3 Transcription Factor; C442759:ginsenoside Rb1