Key result
GCIP-27 at doses of 30 and 90 μg/kg significantly improved cardiac function, including ejection fraction and stroke volume, and reduced myocardial injury in rats with doxorubicin-induced heart failure.
Why the study?
Does GCIP-27 improve cardiac function and alleviate remodeling in rats with doxorubicin-induced heart failure?
Does GCIP-27 improve cardiac function and alleviate remodeling in rats with doxorubicin-induced heart failure?
The Gαq mimetic peptide GCIP-27 effectively ameliorates doxorubicin-induced heart failure and adverse remodeling in rats, suggesting a potential novel therapeutic target.
BACKGROUND: Gαq protein carboxyl terminus imitation polypeptide (GCIP)-27 has been shown to alleviate pathological cardiomyocyte hypertrophy induced by various factors. Pathological cardiac hypertrophy increases the morbidity and mortality of cardiovascular diseases while it compensates for poor heart function. This study was designed to investigate the effects of GCIP-27 on heart function in rats with heart failure induced by doxorubicin. METHODS AND RESULTS: Forty-eight rats were randomly divided into the following six groups receiving vehicle (control), doxorubicin (Dox), losartan (6 mg/kg, i.g.) and three doses of GCIP-27 (10, 30, 90 μg/kg; i.p., bid), respectively. Heart failure was induced by Dox, which was administered at a 20 mg/kg cumulative dose. After 10 weeks of treatment, we observed that GCIP-27 (30, 90 μg/kg) significantly increased ejection fraction, fraction shortening, stroke volume and sarcoplasmic reticulum Ca2+ ATPase activity of Dox-treated hearts. Additionally, GCIP-27 decreased myocardial injury, heart weight index and left ventricular weight index, fibrosis and serum cardiac troponin-I concentration in Dox-treated mice. Immunohistochemistry, western blotting and real-time PCR experiments indicated that GCIP-27 (10-90 μg/kg) could markedly upregulate the protein expression of myocardial α-myosin heavy chain (MHC), Bcl-2, protein kinase C (PKC) ε and phosphorylated extracellular signal-regulated kinase (p-ERK) 1/2 as well as the mRNA expression of α-MHC, but downregulated the expression of β-MHC, Bax and PKC βII, and the mRNA expression levels of β-MHC in Dox-treated mice. It was also found that GCIP-27 (30, 90 μg/L) decreased cell size and protein content of cardiomyocytes significantly in vitro by comparison of Dox group. CONCLUSIONS: GCIP-27 could effectively ameliorate heart failure development induced by Dox. PKC-ERK1/2 signaling might represent the underlying mechanism of the beneficial effects of GCIP-27.
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Lu et al. (2015) studied Chronic heart failure (n=48). GCIP-27 vs. Doxorubicin alone or Losartan was evaluated on Cardiac function (ejection fraction, fraction shortening, stroke volume) (p=<0.05). GCIP-27 at doses of 30 and 90 μg/kg significantly improved cardiac function, including ejection fraction and stroke volume, and reduced myocardial injury in rats with doxorubicin-induced heart failure.
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