β₁- and β₂-adrenergic Receptor Haplotypes Regulate Therapeutic Responses to Placebo and the Biased Ligand β-blocker Bucindolol.

ABSTRACT:

Background

ADRB1 and ADRB2, encoding cardiac myocyte β₁- and β₂-adrenergic receptors (ARs) that mediate pathologic myocardial remodeling in response to chronically increased signaling, contain N-terminus haplotype variants capable of influencing agonist- or biased ligand-induced receptor internalization that uncouples canonical signaling and initiates EGFR/ERK1/2 cardioprotection.

Methods

In two heart failure (HF) clinical trial genetic substudies we investigated effects of internalizing vs. internalization-resistant ADRB1/ADRB2 haplotypes on clinical or biomarker responses to the biased ligand β-blocker bucindolol vs. placebo or vs. the nonbiased β₁-antagonist metoprolol, and in haplotyped isolated human heart pre

SUBMITTER: Carroll IA 

PROVIDER: S-EPMC12440051 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature