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

Right ventricular hypertrophy Therapeutic effect
DOI: 10.3389/fcvm.2021.683436 Publication Date: 2021-06-17T08:49:10Z
ABSTRACT
Background: Previously, we invented a therapeutic vaccine targeting the endothelin-A receptor (termed ETRQβ-002). ETRQβ-002 successfully prevented remodeling of pulmonary arterioles (PAs) and right ventricle (RV) without significant immune-mediated damage in experimental arterial hypertension (PAH) mice models. Objective: Here, aim to further evaluate long-term effects ETRQβ-002. Methods: PAH model was induced by combination subcutaneous injection with Sugen5416 chronic hypoxic conditions (10% O 2 ). were immunized at different time points, experiment lasted for 21 weeks. Hemodynamic, histological, biochemical analyses conducted Results: We demonstrated that titer specific antibody against ETR-002 could be maintained chronically after periodic booster immunization mice. Long-term reduction ventricular systolic pressure amelioration PA confirmed. Moreover, found also exerted antiproliferation, anti-inflammation, antifibrosis remodeling. Besides, durably limited pathological RV hypertrophy fibrosis. Finally, no observed hepatic or renal function pathology liver kidney during administration Conclusion: Our findings indicate provides Sugen/hypoxia-induced animals offers promising clinical prospect treatment.
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