Distinct Mechanisms of β-Arrestin-Biased Agonist and Blocker of AT1R in Preventing Aortic Aneurysm and Associated Mortality.

ABSTRACT:

Background

Aortic aneurysm (AA) is a "silent killer" human disease with no effective treatment. Although the therapeutic potential of various pharmacological agents have been evaluated, there are no reports of β-arrestin-biased AT1R (angiotensin-II type-1 receptor) agonist (TRV027) used to prevent the progression of AA.

Methods

We tested the hypothesis that TRV027 infusion in AngII (angiotensin II)-induced mouse model of AA prevents AA. High-fat-diet-fed ApoE (apolipoprotein E gene)-null mice were infused with AngII to induce AA and co-infused with TRV027 and a clinically used AT1R blocker Olmesartan to prevent AA. Aortas explanted from different ligand infusion groups were compared with assess different grades of AA or lack of AA.

Results

AngII produced AA in ≈67% ma

SUBMITTER: Jara ZP 

PROVIDER: S-EPMC9852074 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature