Recombinant human brain natriuretic peptide therapy combined with bone mesenchymal stem cell transplantation for treating heart failure in rats

Abstract

This study aimed to investigate the effects of combined recombinant human brain natriuretic peptide (rhBNP) therapy and bone mesenchymal stem cell (BMSC) transplantation on cell survival in myocardial tissues and on heart function in a rat model of heart failure (HF). Rat BMSCs were isolated, amplified and adherent cultured in vitro. A rat model of HF was established via the intraperitoneal injection of doxorubicin (Adriamycin). The rats were randomly divided into normal, HF, BMSC, rhBNP and BMSC plus rhBNP groups. The BMSCs were administered once via tail vein injection and rhBNP was infused via the jugular vein. Echocardiography and polygraphy were used to evaluate heart function. An enzyme linked immunosorbent assay was used to detect the changes in brain natriuretic peptide (BNP) concentration prior to and following intervention. Western blot analysis was used to detect the expression of the myocardium specific proteins GATA-binding protein 4 (GATA-4), connexin 43 (Cx43) and cardiac troponin I (cTnI). The results of cardiac echocardiography and the hemodynamic data show that various indicators of left ventricular systolic function in the BMSC plus rhBNP group were significantly improved compared with those in the other groups (P<0.05). No significant differences in the improvement of cardiac function were observed between the BMSC and rhBNP groups (P>0.05). Following treatment, a significant difference in BNP levels was observed between the BMSC plus rhBNP and the BMSC groups (P<0.05). The GATA-4, Cx43 and cTnI expression levels in the BMSC plus rhBNP group were higher than those in the BMSC group. Compared with rhBNP treatment, BMSC transplantation alone does not significantly improve heart function. However, combining rhBNP therapy and BMSC transplantation increases the expression levels of GATA-4 and other proteins to improve cardiac systolic and diastolic function. Copyright © 2013 Spandidos Publications Ltd.