GCIP attenuates DOCA/salt-induced cardiac hypertrophy and fibrosis in mice

Abstract

Objective To determine the effects of improvement of G alpha q-protein carboxyl terminus imitation polypeptide (GCIP) on deoxycorticosterone acetate (DOCA)/salt-induced cardiac hypertrophy and fibrosis in mice. Methods After unilateral nephrectomy, 61 male C57BL/6 mice were randomly divided into control group (n=10), DOCA-salt group (n=14), GCIP 0.1 mg/kg group (n=12), GCIP 0.3 mg/kg group (n=12) and GCIP 1.0 mg/kg group (n=13). Except control group, the mice in other groups were given subcutaneous injection of deoxycorticosterone acetate (100 mg/kg) every 2 d and replacement of drinking water with 1% NaCl to prepare cardiac hypertrophy and fibrosis model. At the same time, the GCIP groups were given subcutaneous injection of GCIP at corresponding doses, twice a day. Their survival rate was observed every day. The blood pressure (BP) was measured by a tail-cuff blood pressure system every 4 days, and cardiac function was assessed by echocardiography. Hematoxylin-Eosin (HE) and wheat germ agglutinin (WGA) staining in heart tissue were used to evaluate cardiac hypertrophy. Sirius red staining in heart tissue was used to evaluate cardiac fibrosis. Moreover, Western blot analysis was used to detect the expression of α-SMA, p38 and ERK1/2. Results Compared with the control group, the DOCA-salt group had obviously decreased survival rate (43%), increased BP level (25.61%), decreased left ventricular systolic function, and obvious hypertrophy and fibrosis in hear tissue (P < 0.05). GCIP treatment significantly increased survival rate (35%), decreased BP (12.40%), improved left ventricular systolic function and attenuated cardiac hypertrophy and fibrosis (P < 0.05). Furthermore, the expression of α-SMA and phosphorylation of p38 and ERK1/2 were increased in the heart tissue of the DOCA/salt-treated mice (P < 0.05), while GCIP treatment reversed above phenomena (P < 0.05). Conclusion GCIP can effectively inhibit DOCA/salt-induced hypertensive cardiac hypertrophy and fibrosis, which is associated with its inhibition on phosphorylation of p38 and ERK1/2.

Keywords

• polypeptide drugs
• salt sensitive hypertension
• cardiac hypertrophy
• cardiac fibrosis