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

Area of Science:

• Cardiovascular Research
• Pulmonary Medicine
• Regenerative Medicine

Background:

• Pulmonary arterial hypertension (PAH) is a severe condition impacting the pulmonary vasculature and right ventricle (RV).
• Current treatments for PAH are limited, highlighting the need for novel therapeutic strategies.
• The neuregulin-1 (NRG-1)/ErbB signaling pathway is implicated in heart failure and cardiac dysfunction.

Purpose of the Study:

• To investigate the therapeutic potential of recombinant human NRG-1 (rhNRG-1) in mitigating right ventricular hypertrophy (RVH) and dysfunction in a rat model of monocrotaline (MCT)-induced pulmonary arterial hypertension (PAH).
• To assess the impact of rhNRG-1 on pulmonary vascular remodeling and endothelial function in the context of PAH.

Main Methods:

• Male Wistar rats were administered monocrotaline (MCT) to induce PAH or underwent pulmonary artery banding (PAB) to simulate pressure overload.
• Animals were treated with rhNRG-1 or vehicle, with treatment commencing two weeks post-MCT administration or PAB.
• Evaluations included assessments of RV hypertrophy, cardiac function, pulmonary vascular remodeling, and endothelial function markers.

Main Results:

• MCT-induced PAH led to significant pulmonary arterial and RV remodeling, dysfunction, and cardiac damage markers.
• rhNRG-1 treatment attenuated RV hypertrophy, improved RV function, and reduced RV disease markers.
• rhNRG-1 administration decreased pulmonary vascular remodeling and ameliorated endothelial dysfunction in the MCT-induced PAH model.
• The beneficial anti-remodeling effects of rhNRG-1 were further confirmed in the PAB model, reducing RVH.

Conclusions:

• rhNRG-1 treatment effectively attenuates pulmonary arterial and right ventricular remodeling and dysfunction in a rat model of MCT-induced PAH.
• rhNRG-1 demonstrates direct anti-remodeling properties on the pressure-overloaded right ventricle.
• These findings suggest rhNRG-1 as a potential therapeutic agent for PAH and associated RV complications.