Neuregulin-1/erbB-Activation Improves Cardiac Function and Survival in Models of Ischemic, Dilated, and Viral Cardiomyopathy

Liu, Xifu; Gu, Xueping; Li, Zhaoming; Li, Xinyan; Li, Hui; Chang, Jianjie; Chen, Ping; Jin, Jing; Xi, Bing; Chen, Denghong; Lai, Donna; Graham, Robert M.; Zhou, Meijuan

doi:10.1016/j.jacc.2006.05.057

Cited by 247 publications

(252 citation statements)

References 24 publications

(32 reference statements)

Supporting

Mentioning

241

Contrasting

Unclassified

Order By: Relevance

“…In fact, we have shown that these MPs persist in heart tissue for at least 90 days following implantation, favoring long-term growth factor therapy [38]. The importance of this sustained release is supported by the fact that previous studies analyzing intravenous injection of free NRG1 did not observe improvements in infarct size [22], supporting the benefit of using PLGA MPs for delivery. Furthermore, while MPs were implanted by direct injection in this study, the size of the particles employed should allow for delivery through a less invasive procedure, such as using a NOGAguided catheter.…”

Section: Discussionmentioning

confidence: 70%

“…Consistent with this idea, it is known that FGF1 regulates cardiac remodeling by exerting a protective and proliferative effect after MI [18,19]. On the other hand, neuregulins play crucial roles in the adult cardiovascular system by inducing structural organization of sarcomeres, cell integrity, cell-cell adhesion [20], cell survival [21,22] and angiogenesis [23]. In fact, several studies using animal models of heart failure have demonstrated the therapeutic benefits of neuregulins, which improved cardiac performance, attenuated disease markers, and prolonged animal survival [24,25].…”

Section: Introductionmentioning

confidence: 80%

See 1 more Smart Citation

Controlled delivery of fibroblast growth factor-1 and neuregulin-1 from biodegradable microparticles promotes cardiac repair in a rat myocardial infarction model through activation of endogenous regeneration

Formiga

Pelacho

Garbayo

et al. 2014

Journal of Controlled Release

100

View full text Add to dashboard Cite

Acidic fibroblast growth factor (FGF1) and neuregulin-1 (NRG1) are growth factors involved in cardiac development and regeneration. Microparticles (MPs) mediate cytokine sustained release, and can be utilized to overcome issues related to the limited therapeutic protein stability during systemic administration. We sought to examine whether the administration of microparticles (MPs) containing FGF1 and NRG1 could promote cardiac regeneration in a myocardial infarction (MI) rat model. We investigated the possible underlying mechanisms contributing to the beneficial effects of this therapy, especially those linked to endogenous regeneration. FGF1-and NRG1-loaded MPs were prepared using a multiple emulsion solvent evaporation technique. Seventy-three female Sprague-Dawley rats underwent permanent left anterior descending coronary artery occlusion, and MPs were intramyocardially injected in the peri-infarcted zone four days later. Cardiac function, heart tissue remodeling, revascularization, apoptosis, cardiomyocyte proliferation, and stem cell homing were evaluated one week and three months after treatment. MPs were shown to efficiently encapsulate FGF1 and NRG1, releasing the bioactive proteins in a sustained manner. Three months after treatment, a statistically significant improvement in cardiac function was detected in rats treated with growth factor-loaded MPs (FGF1, NRG1, or FGF1/NRG1). The therapy led to inhibition of cardiac remodeling with smaller infarct size, a lower fibrosis degree and induction of tissue revascularization. Cardiomyocyte proliferation and progenitor cell recruitment was detected. Our data support the therapeutic benefit of NRG1 and FGF1 when combined with protein delivery systems for cardiac regeneration. This approach could be scaled up for use in preclinical and clinical studies.

show abstract

Section: Discussionmentioning

confidence: 70%

Section: Introductionmentioning

confidence: 80%

Controlled delivery of fibroblast growth factor-1 and neuregulin-1 from biodegradable microparticles promotes cardiac repair in a rat myocardial infarction model through activation of endogenous regeneration

Formiga

Pelacho

Garbayo

et al. 2014

Journal of Controlled Release

100

View full text Add to dashboard Cite

show abstract

“…Recombinant NRG1 (beta-2a; Zensun Sci and Tech, Shanghai, China) [5] at 50 g/kg body weight or an equivalent volume of 0.9% NaCl (sodium chloride) was administered by i.p. injection three times a week for 8 weeks (n = 8 for each group).…”

Section: Nrg1 Treatmentmentioning

confidence: 99%

Neuregulin 1 affects leptin levels, food intake and weight gain in normal-weight, but not obese, db/db mice

Ennequin

Caillaud

Chavanelle

et al. 2015

Diabetes & Metabolism

View full text Add to dashboard Cite

Aim. -Studies in vitro have highlighted the potential involvement of neuregulin 1 (NRG1) in the regulation of energy metabolism. This effect has also been suggested in vivo, as intracerebroventricular injection of NRG1 reduces food intakes and weight gain in rodents. Thus, it was hypothesised that NRG1 might affect serum leptin levels in mice.Methods. -Weight, food intakes, energy expenditure, spontaneous physical activity and serum leptin levels were evaluated in normal-weight C57BL/6JRJ mice following intraperitoneal administration of NRG1 (50 g/kg, three times/week) or saline for 8 weeks. Based on the results of this first experiment, leptin-resistant obese db/db mice were then given NRG1 for 8 weeks.Results. -Leptin serum concentrations were six times higher in C57BL/6JRJ mice treated with NRG1 than in the animals given saline. NRG1 treatment also reduced weight gain by 10% and food intakes by 15% compared with saline treatment, while energy expenditure remained unchanged. In db/db mice, serum leptin concentrations, weight gain, food intakes, energy expenditure and spontaneous physical activity were not altered by NRG1 treatment.Conclusion. -The decrease in food intakes and weight gain associated with NRG1 treatment in C57BL/6JRJ mice may be partly explained by increased leptin levels, whereas db/db mice were not affected by the treatment, suggesting resistance to NRG1 in this pathological state.

show abstract

“…Neuregulin1 proteins improve cardiac function in doxorubicin-treated animals (Liu et al, 2005;Liu et al, 2006;Bian et al, 2009). Comparing the two studies, we used recombinant human glial growth factor 2 (GGF2), and a subacute doxorubicin cardiotoxicity mouse model (doxorubicin, 20 mg/kg, i.p.…”

Section: Our Laboratory and Liu Et Al Further Demonstrated That Injementioning

confidence: 99%

“…Recombinant Neuregulin1 was injected i.v. daily for the first 7 days using the dosage of 20µg/kg/day (Liu et al, 2006). Despite the different isoforms of Neuregulin1, the dosage, the route of drug administration and the animal models used, both studies showed that injections of recombinant Neuregulin1 significantly improved survival and cardiac systolic function in doxorubicin-injured mice and rats.…”

Section: Our Laboratory and Liu Et Al Further Demonstrated That Injementioning

confidence: 99%

Neuregulin1-ErbB Signaling in Doxorubicin-Induced Cardiotoxicity

Goukassian¹,

Morgan²,

Yan³

2012

Cardiotoxicity of Oncologic Treatments

View full text Add to dashboard Cite

Neuregulin-1/erbB-Activation Improves Cardiac Function and Survival in Models of Ischemic, Dilated, and Viral Cardiomyopathy

Abstract: These beneficial effects make rhNRG-1 promising as a broad-spectrum therapeutic for the treatment of heart failure due to a variety of common cardiac diseases.

Cited by 247 publications

References 24 publications

Controlled delivery of fibroblast growth factor-1 and neuregulin-1 from biodegradable microparticles promotes cardiac repair in a rat myocardial infarction model through activation of endogenous regeneration

Controlled delivery of fibroblast growth factor-1 and neuregulin-1 from biodegradable microparticles promotes cardiac repair in a rat myocardial infarction model through activation of endogenous regeneration

Neuregulin 1 affects leptin levels, food intake and weight gain in normal-weight, but not obese, db/db mice

Neuregulin1-ErbB Signaling in Doxorubicin-Induced Cardiotoxicity

Contact Info

Product

Resources

About