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

• Type: Article in International Scientific Journal
• Date: 2016

Authors

Mendes-Ferreira, P. (Author) FMUP; Maia-Rocha, C. (Author) FMUP; Adão, R. (Author) FMUP; Mendes, M.J. (Author) FMUP; Santos-Ribeiro, D. (Author) FMUP; Silvana Alves, B. (Author) FMUP; Cerqueira, R.J. (Author) FMUP; Castro-Chaves, P. (Author) FMUP; Lourenço, A.P. (Author) FMUP; Keulenaer, G. (Author) FMUP; Leite Moreira, A. (Author) FMUP; Brás-Silva, Carmen (Author) FCNAUP

Journal

Title: Cardiovascular Research

Vol. 109 No. 1

Pages: 44-54

ISSN: 0008-6363

Publisher: Oxford University Press

Indexing

ISI Web of Knowledge - 30 Citations

ISI Web of Science

Scopus - 30 Citations

Scientific classification

CORDIS: Health sciences

FOS: Medical and Health sciences

Other information

Authenticus ID: P-00K-0M3

DOI: 10.1093/cvr/cvv244

Abstract (EN): 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 ¼ 78) were injected with MCT (60 mg/kg, s.c.) or saline and treated with rhNRG- 1 (40 mg/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 Pulmonary hypertension ¿ Right ventricular function ¿ Neuregulin ¿ Endothelial dysfunction ¿ Cardiac hypertrophy

Language: English

Type (Professor's evaluation): Scientific

Notes: Epub 2015.10.15. <a href="http://gateway.isiknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=Alerting&SrcApp=Alerting&DestApp=WOS&DestLinkType=FullRecord&KeyUT=000368414600007">Indexado na ISI Web of Science</a>