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Silvana Alves, B.
Leite Moreira, A.
|Title:||Neuregulin-1 improves right ventricular function and attenuates experimental pulmonary arterial hypertension|
|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 deregulatedduring heart failure, and treatment with recombinant human NRG-1 (rhNRG-1) has been shown to be beneficial inanimal models and in patients with left ventricular (LV) dysfunction. This study aimed to evaluate the effects ofrhNRG-1 in RV function and pulmonary vasculature in monocrotaline (MCT)-induced PAH and RV hypertrophy(RVH).Methods and resultsMale wistar rats (7- to 8-weeks old, n Œ 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 submittedto pulmonary artery banding (PAB) or sham surgery, and followed the same protocol. MCT administration resultedin the development of PAH, pulmonary arterial and RV remodelling, and dysfunction, and increased RV markers of cardiacdamage. Treatment with rhNRG-1 attenuated RVH, improved RV function, and decreased RV expression of diseasemarkers. Moreover, rhNRG-1 decreased pulmonary vascular remodelling and attenuated MCT-inducedendothelial dysfunction. The anti-remodelling effects of rhNRG-1 were confirmed in the PAB model, whererhNRG-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-inducedPAH and has direct anti-remodelling effects on the pressure-overloaded RV.Keywords Pulmonary hypertension Right ventricular function Neuregulin Endothelial dysfunction Cardiachypertrophy|
|Subject:||Ciências da Saúde, Ciências médicas e da saúde|
Health sciences, Medical and Health sciences
|Scientific areas:||Ciências médicas e da saúde|
Medical and Health sciences
|Document Type:||Artigo em Revista Científica Internacional|
|Appears in Collections:||FCNAUP - Artigo em Revista Científica Internacional|
FMUP - Artigo em Revista Científica Internacional
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