ABSTRACT
Objective To investigate the effect of cellular repressor of E1A stimulated genes (CREG1) on cardiac function in mouse with myocardial fibrosis. Methods CREG1 knockout mice (CREG1+/-) and CREG1 wild-type mice (CREG1+/+) were used to reproduce the model of myocardial fibrosis by subcutaneous pump burying of angiotensin Ⅱ (AngⅡ). After being stimulated with AngⅡ for 14 days, myocardial fibrosis was verified by HE staining and Masson trichrome staining. Western blotting and immunohistochemistry were used to detect the expression of CREG1 in myocardium before stimulation and 3, 7, 14 days after the AngⅡ stimulation. The cardiac function was evaluated by echocardiography after AngⅡ stimulation for 14 days. The CREG+/+ mice were given AngⅡ for 14 days, and at the same time recombinant CREG1 protein [respectively 15, 30, 60 and 300μg/(kg.d), intraperitoneal (IP) injections] (treatment group) and NaCl (control group) were administered for treatment, and then cardiac function and myocardiac apoptosis were examined. Results Western blotting and immunohistochemistry showed that the expression of CREG1 in heart tissue was significantly lower in CREG+/-mice than in CREG+/+ mice (P<0.05). After AngⅡ stimulation for 3, 7 and 14 days, the expression of CREG1 in heart tissue declined significantly in both CREG+/-and CREG+/+ mice (P<0.05), especially in CREG+/-mice (P<0.01). With HE and Masson staining, it was also found that CREG1 deficiency aggravated myocardial fibrosis and cardiac function deterioration in response to AngⅡ stimulation (P<0.05). Conversely, exogenous infusion of recombinant CREG1 protein significantly inhibited the occurrence of myocardial apoptosis (P<0.05), thus ameliorated cardiac function (P<0.05). Conclusions CREG1 deficiency may aggravate the deterioration of cardiac function in mouse with myocardial fibrosis induced by AngⅡ stimulation. The deterioration of cardiac function can be improved by administration of exogenous recombinant CREG1 protein.