Therapeutic efficacy of the novel selective RNA polymerase I inhibitor CX-5461 on pulmonary arterial hypertension and associated vascular remodelling.

ABSTRACT:

Background and purpose

CX-5461 is a novel selective RNA polymerase I (Pol I) inhibitor. Previously, we found that CX-5461 could inhibit pathological arterial remodelling caused by angioplasty and transplantation. In the present study, we explored the pharmacological effects of CX-5461 on experimental pulmonary arterial hypertension (PAH) and PAH-associated vascular remodelling.

Experimental approach

PAH was induced in Sprague-Dawley rats by monocrotaline or Sugen/hypoxia.

Key results

We demonstrated that CX-5461 was well tolerated for in vivo treatments. CX-5461 prevented the development of pulmonary arterial remodelling, perivascular inflammation, pulmonary hypertension, and improved survival. More importantly, CX-5461 partly reversed established pulmonary hypertensi

SUBMITTER: Xu X 

PROVIDER: S-EPMC9328314 | biostudies-literature | 2021 Apr

REPOSITORIES: biostudies-literature