Study of human datasets, Ang II-treated mice and cardiomyocytes links altered DRD1 to atrial fibrillation-related stress

A study combining human cardiac transcriptomic datasets, an angiotensin II (Ang II) mouse model and HL-1 cardiomyocytes found that dopamine receptor D1 (DRD1) expression was altered in epicardial adipose tissue and reduced in myocardial tissue from patients with atrial fibrillation (AF) compared with sinus rhythm controls. In the mouse model, atrial DRD1 expression was also lower after chronic Ang II infusion, alongside increased AF inducibility and duration. The reported abstract does not establish that reduced DRD1 caused the greater AF susceptibility observed in the animals.

For the human analyses, the researchers examined DRD1 expression in the GSE135445 epicardial adipose tissue dataset and independently in the GSE41177 myocardial transcriptomic dataset. They also assessed DRD1 expression and AF-associated phenotypes in C57BL/6 mice subjected to chronic Ang II infusion. These approaches linked expression changes with experimental atrial remodeling but did not directly test whether manipulating DRD1 in vivo would change AF susceptibility.

Cell experiments provided a functional assessment. In HL-1 cardiomyocytes, Ang II reduced DRD1 expression, whereas DRD1 overexpression increased phosphorylation of PI3K/Akt. Overexpression also attenuated Ang II-induced reductions in cell viability, increases in lactate dehydrogenase release and hypertrophic responses, as well as increases in reactive oxygen species generation, oxidative stress and signaling associated with the NLRP3 inflammasome. These findings describe a protective effect of increased DRD1 expression against Ang II-induced cellular stress under the tested experimental conditions.

The researchers evaluated the contribution of PI3K/Akt signaling with LY294002, which partially attenuated the effects associated with DRD1 overexpression. On the basis of this cell-model intervention, the authors concluded that PI3K/Akt signaling contributed to the observed protection, while noting that the molecular pathway was not necessarily responsible for the entire effect. The work is a combined human-data, animal and cell study, and the available abstract does not provide sample sizes, effect estimates or statistical details. Its principal limitation is that the causal regulation of AF susceptibility by DRD1 in vivo remained unestablished; the reported cell findings therefore do not demonstrate a clinical benefit or establish a treatment effect in people with AF.

Subject of Research: DRD1 expression and PI3K/Akt signaling in atrial fibrillation-associated tissue and experimental cardiomyocyte stress

Article Title: Dopamine receptor D1 is altered in atrial fibrillation-associated tissues and modulates Ang II-induced cardiomyocyte stress partly through PI3K/Akt signaling

Article References: Shu, W., & Ning, Z. (2026). Dopamine receptor D1 is altered in atrial fibrillation-associated tissues and modulates Ang II-induced cardiomyocyte stress partly through PI3K/Akt signaling. Molecular Biology Reports, 53(1), Article 1581. https://doi.org/10.1007/s11033-026-12755-1

Image Credits: AI Generated

DOI: 10.1007/s11033-026-12755-1

Keywords: dopamine receptor D1, atrial fibrillation, cardiomyocyte stress, angiotensin II, PI3K/Akt signaling, oxidative stress, NLRP3 inflammasome, epicardial adipose tissue, mouse model, Dopamine, receptor, altered