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Cardiovasc Res. 2016 Jan 1;109(1):44-54. doi: 10.1093/cvr/cvv244. Epub 2015 Oct 26.

Neuregulin-1 improves right ventricular function and attenuates experimental pulmonary arterial hypertension.

Author information

1
Department of Physiology and Cardiothoracic Surgery, Faculty of Medicine, Cardiovascular Research and Development Centre, University of Porto, Al. Prof. Hernâni Monteiro, 4200-319 Porto, Portugal.
2
Laboratory of Physiology, University of Antwerp, Antwerpen, Belgium.
3
Department of Physiology and Cardiothoracic Surgery, Faculty of Medicine, Cardiovascular Research and Development Centre, University of Porto, Al. Prof. Hernâni Monteiro, 4200-319 Porto, Portugal Faculty of Nutrition and Food Sciences, University of Porto, Porto, Portugal carmensb@med.up.pt.

Abstract

AIMS:

Pulmonary arterial hypertension (PAH) is a serious disease that affects both the pulmonary vasculature and the right ventricle (RV). Current treatment options are insufficient. The cardiac neuregulin (NRG)-1/ErbB system is deregulated during heart failure, and treatment with recombinant human NRG-1 (rhNRG-1) has been shown to be beneficial in animal models and in patients with left ventricular (LV) dysfunction. This study aimed to evaluate the effects of rhNRG-1 in RV function and pulmonary vasculature in monocrotaline (MCT)-induced PAH and RV hypertrophy (RVH).

METHODS AND RESULTS:

Male wistar rats (7- to 8-weeks old, n = 78) were injected with MCT (60 mg/kg, s.c.) or saline and treated with rhNRG-1 (40 µg/kg/day) or vehicle for 1 week, starting 2 weeks after MCT administration. Another set of animals was submitted to pulmonary artery banding (PAB) or sham surgery, and followed the same protocol. MCT administration resulted in the development of PAH, pulmonary arterial and RV remodelling, and dysfunction, and increased RV markers of cardiac damage. Treatment with rhNRG-1 attenuated RVH, improved RV function, and decreased RV expression of disease markers. Moreover, rhNRG-1 decreased pulmonary vascular remodelling and attenuated MCT-induced endothelial dysfunction. The anti-remodelling effects of rhNRG-1 were confirmed in the PAB model, where rhNRG-1 treatment was able to attenuate PAB-induced RVH.

CONCLUSION:

rhNRG-1 treatment attenuates pulmonary arterial and RV remodelling, and dysfunction in a rat model of MCT-induced PAH and has direct anti-remodelling effects on the pressure-overloaded RV.

KEYWORDS:

Cardiac hypertrophy; Endothelial dysfunction; Neuregulin; Pulmonary hypertension; Right ventricular function

PMID:
26503987
DOI:
10.1093/cvr/cvv244
[Indexed for MEDLINE]

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