An extensive ß1-adrenergic receptor gene signaling network regulates molecular remodeling in dilated cardiomyopathies.
JCI Insight
; 8(16)2023 08 22.
Article
em En
| MEDLINE
| ID: mdl-37606047
ABSTRACT
We investigated the extent, biologic characterization, phenotypic specificity, and possible regulation of a ß1-adrenergic receptor-linked (ß1-AR-linked) gene signaling network (ß1-GSN) involved in left ventricular (LV) eccentric pathologic remodeling. A 430-member ß1-GSN was identified by mRNA expression in transgenic mice overexpressing human ß1-ARs or from literature curation, which exhibited opposite directional behavior in interventricular septum endomyocardial biopsies taken from patients with beta-blocker-treated, reverse remodeled dilated cardiomyopathies. With reverse remodeling, the major biologic categories and percentage of the dominant directional change were as follows metabolic (19.3%, 81% upregulated); gene regulation (14.9%, 78% upregulated); extracellular matrix/fibrosis (9.1%, 92% downregulated); and cell homeostasis (13.3%, 60% upregulated). Regarding the comparison of ß1-GSN categories with expression from 19,243 nonnetwork genes, phenotypic selection for major ß1-GSN categories was exhibited for LV end systolic volume (contractility measure), ejection fraction (remodeling index), and pulmonary wedge pressure (wall tension surrogate), beginning at 3 months and persisting to study completion at 12 months. In addition, 121 lncRNAs were identified as possibly involved in cis-acting regulation of ß1-GSN members. We conclude that an extensive 430-member gene network downstream from the ß1-AR is involved in pathologic ventricular remodeling, with metabolic genes as the most prevalent category.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Produtos Biológicos
/
Cardiomiopatia Dilatada
Limite:
Animals
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Humans
Idioma:
En
Revista:
JCI Insight
Ano de publicação:
2023
Tipo de documento:
Article