Frontiers in Cardiovascular Medicine (Jun 2021)

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

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

DOI
https://doi.org/10.3389/fcvm.2021.683436
Journal volume & issue
Vol. 8

Abstract

Read online

Background: Previously, we invented a therapeutic vaccine targeting the endothelin-A receptor (termed ETRQβ-002). ETRQβ-002 successfully prevented the remodeling of pulmonary arterioles (PAs) and right ventricle (RV) without significant immune-mediated damage in experimental pulmonary arterial hypertension (PAH) mice models.Objective: Here, we aim to further evaluate the long-term effects of ETRQβ-002.Methods: PAH mice 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 and amelioration of PA remodeling by ETRQβ-002 were confirmed. Moreover, we found that ETRQβ-002 also exerted antiproliferation, anti-inflammation, and antifibrosis effects in PA remodeling. Besides, ETRQβ-002 durably limited pathological RV hypertrophy and fibrosis. Finally, no immune-mediated damage was observed in hepatic or renal function or by pathology in liver and kidney during the long-term administration of ETRQβ-002.Conclusion: Our findings indicate that ETRQβ-002 provides long-term therapeutic effects in Sugen/hypoxia-induced PAH animals and offers a promising clinical prospect for PAH treatment.

Keywords