Beta-3 adrenergic receptor overexpression reverses aortic stenosis-induced heart failure and restores balanced mitochondrial dynamics.

ABSTRACT: Aortic stenosis (AS) is associated with left ventricular (LV) hypertrophy and heart failure (HF). There is a lack of therapies able to prevent/revert AS-induced HF. Beta3 adrenergic receptor (β3AR) signaling is beneficial in several forms of HF. Here, we studied the potential beneficial effect of β3AR overexpression on AS-induced HF. Selective β3AR stimulation had a positive inotropic effect. Transgenic mice constitutively overexpressing human β3AR in the heart (c-hβ3tg) were protected from the development of HF in response to induced AS, and against cardiomyocyte mitochondrial dysfunction (fragmented mitochondria with remodeled cristae and metabolic reprogramming featuring altered substrate use). Similar beneficial effects were observed in wild-type mice inoculated with adeno-associated v

SUBMITTER: Pun-Garcia A 

PROVIDER: S-EPMC9708808 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature