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

Abstract

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. IntroductionAcute myocardial infarction is one of main causes of cardiac insufficiency. When complicated by decompensated heart failure, it is one of the primary causes of mortality from coronary heart disease. Certain patients present with acute decompensated heart failure despite receiving standardized anticoagulation and anti-ischemia treatment (including thrombolysis and emergency percutaneous coronary intervention), which necessitates the use of an appropriate cardiotonic to improve the clinical symptoms and prognosis. Recombinant human brain natriuretic peptide (rhBNP) is used to treat acute decompensated heart failure (1-3).Bone mesenchymal stem cells (BMSCs) are of particular interest to researchers due to their potential to differentiate into myocardial cells, which are convenient and have low tendency to cause immunological reactions and rejection (4-6). In recent years, animal experiments involving BMSC transplantation have been successfully conducted and transplanted BMSCs have been confirmed to improve cardiac function (7-10). However, the results of previous clinical studies using BMSCs are unsatisfactory. BMSCs for use...

Retracted: rhBNP therapy can improve clinical outcomes and reduce in‐hospital mortality compared with dobutamine in heart failure patients: a meta‐analysis

“…However, increased myocardial contractility, the adverse effects of high doses of dobutamine and sensitivity to drugs causes rapid rise in heart rate and blood pressure, and is a poor prognostic indicator in HF patients treated with dobutamine . Our study is consistent with Zhang and his colleagues who demonstrated that rhBNP lacks the positive inotropic properties to maintain elevated myocardial oxygen consumption, while dobutamine increases oxygen consumption, which is detrimental in patients with abnormal cardiac function . In addition, both Pan et al and Arnold et al .…”

“…In addition, by elevating glomerular filtration rate and inhibiting sodium reabsorption in kidney proximal tubules, rhBNP displays high diuretic/natriuretic activity and suppresses vasoactive peptide production [51,52]. Importantly, rhBNP is an antagonist of the renin angiotensin aldosterone system, and prevents its excess activation and reverses the adverse effects of renin, aldosterone, endothelin and vasopressin [53]. We propose that the superior clinical outcomes we observed in rhBNP treated HF patients may be related to its lack of positive inotropic effect, which reduces risks associated with increased heart rate and arrhythmia, contrary to dobutamine, and also related to its sensitive regulation of blood pressure/volume and salt balance [31].…”

In vitro differentiation of W8B2+ human cardiac stem cells: gene expression of ionic channels and spontaneous calcium activity

“…The present results also highlight upregulated expression of BNP during W8B2 + CSC differentiation, an effect that was also found during cardiomyocyte differentiation of rat MSCs and monkey embryonic stem cells [31][32][33]. BNP is able to induce cardiomyocyte differentiation of mouse CSCs [34] and improve cardiac function following transplantation of MSCs into a mouse model of heart failure [35]. Recently, Al-Maqtari and colleagues reported that BNP-encoding transcripts were overexpressed when human c-kit + CSCs were induced by some cardiac transcription factors [36].…”

Protective effects of recombinant human brain natriuretic peptide in perioperative period during open heart surgery

“…The results of this study showed that postoperative LVEF were higher than preoperative in the two groups of patients, and the observation group was significantly higher than the control group after 7 days of treatment (P<0.05). Moreover, natriuretic peptide has ability to directly affect myocardial cells, thereby reducing myocardial oxygen consumption, with inhibition of excessive stress reaction of the circulatory system, so as to have a protective effect on the heart ( 17 , 18 ).…”