AUTHOR=Dai Yong , Qiu Zhihua , Ma Wenrui , Li Chang , Chen Xiao , Song Xiaoxiao , Bai Zeyang , Shi Dingyang , Zheng Jiayu , Pan Guangwei , Liao Yuhua , Liao Mengyang , Zhou Zihua 

TITLE=Long-Term Effect of a Vaccine Targeting Endothelin-1 Receptor Type A in Pulmonary Arterial Hypertension

JOURNAL=Frontiers in Cardiovascular Medicine

VOLUME=Volume 8 - 2021

YEAR=2021

URL=https://www.frontiersin.org/journals/cardiovascular-medicine/articles/10.3389/fcvm.2021.683436

DOI=10.3389/fcvm.2021.683436

ISSN=2297-055X

ABSTRACT=Background: Previously, we invented a therapeutic vaccine targeting the endothelin-A receptor (termed ETRQβ-002). ETRQβ-002 successfully prevented the remodeling of pulmonary arterioles (PA) and right ventricle (RV) without significant immune-mediated damage in experimental pulmonary arterial hypertension (PAH) rodent models. 

Objective: Here, we aim to further evaluate the long-term effects of ETRQβ-002.

Methods: PAH rodent model was induced by a combination of subcutaneous injection with Sugen5416 and chronic hypoxic conditions (10% O2). PAH mice were immunized with ETRQβ-002 at different time points, and the experiment lasted for 21 weeks. Hemodynamic, histological, and biochemical analyses were conducted to evaluate the long-term effects of ETRQβ-002.

Results: We demonstrated that the titer of the specific antibody against ETR-002 could be maintained chronically after periodic booster immunization in PAH mice. Long-term reduction of right ventricular systolic pressure (RVSP) and amelioration of PA remodeling by ETRQβ-002 were confirmed. Moreover, we found that ETRQβ-002 also exerted anti-proliferation, anti-inflammation, and anti-fibrosis effects in PA remodeling. Besides, ETRQβ-002 durably limited pathological RV hypertrophy and fibrosis. Finally, no immune-mediated damage was observed in potential targeted organs of PAH mice during the long-term administration of ETRQβ-002.

Conclusion: Our findings indicate that ETRQβ-002 provides long-term therapeutic effects in Sugen/hypoxia (SuHx)-induced PAH animals and offers a promising clinical prospect for PAH treatment.