Differential gene expression in ADGRF5 overexpression versus control in neonatal rat ventricular myocytes

ABSTRACT: G-Protein Coupled Receptors (GPCRs) represent one of the most targeted drug classes in the human genome, accounting for greater than 40% of all FDA-approved drugs, including gold-standard heart failure (HF) therapeutics. However, the second-largest family of GPCRs, known as Adhesion GPCRs (aGPCR), have yet to serve as a clinical target despite increasing evidence of their pathophysiological contributions, representing an area of highly unexplored druggable potential. We identified an aGPCR, known as ADGRF5, to be highly expressed in the left ventricle (LV) of C57BL/6, which we also found increases in response to transaortic constriction (TAC) surgery. To determine the impact of ADGRF5 on cardiac parameters normally or during HF, we generated constitutive cardiomyocyte-specific (αMHC-Cre-driven) ADGRF5 knockout mice (cmF5KO), which displayed normal cardiac structure and function at 12 weeks of age, as assessed via echocardiography, gravimetrics and immunohistochemistry. However, over time cmF5KO mice developed worsened cardiac function and remodeling with increased mortality, even in the absence of pathologic insult, suggesting ADGRF5 provides a homeostatic regulatory function in the heart. To determine the impact of the receptor in vitro, we overexpressed ADGRF5 in neonatal rat ventricular myocytes (NRVMs) versus vehicle controls, and subsequently performed RNA-sequencing to determine differential gene expression. We identified 2039 differentially expressed genes (815 upregulated, 1225 downregulated).

ORGANISM(S): Rattus norvegicus

PROVIDER: GSE324029 | GEO | 2026/03/09

REPOSITORIES: GEO