Gaq Protein Carboxyl Terminus Imitation Polypeptide Gcip-27 Improves Cardiac Function In Chronic Heart Failure Rats

BackgroundGaq 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 ResultsForty-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 mu g/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 mu g/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 mu g/kg) could markedly upregulate the protein expression of myocardial alpha-myosin heavy chain (MHC), Bcl-2, protein kinase C (PKC) epsilon and phosphorylated extracellular signal-regulated kinase (p-ERK) 1/2 as well as the mRNA expression of alpha-MHC, but downregulated the expression of beta-MHC, Bax and PKC beta II, and the mRNA expression levels of beta-MHC in Doxtreated mice. It was also found that GCIP-27 (30, 90 mu g/L) decreased cell size and protein content of cardiomyocytes significantly in vitro by comparison of Dox group.ConclusionsGCIP-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.