DRD1 expression is altered in epicardial adipose tissue and downregulated in myocardial tissue of patients with AF and in experimental atrial remodeling, and DRD1 overexpression protects cardiomyocytes against Ang II-induced stress with PI3K/Akt signaling contributing to this effect.
DRD1 expression was altered in epicardial adipose tissue (EAT) of patients with atrial fibrillation compared to sinus rhythm controls.
DRD1 was downregulated in the myocardial tissue of patients with atrial fibrillation compared to sinus rhythm controls.
DRD1 expression was reduced in the atrial tissue of Ang II-treated mice, which showed increased AF inducibility and duration.
Angiotensin II reduced DRD1 expression in HL-1 cardiomyocytes in vitro.
DRD1 overexpression in HL-1 cardiomyocytes attenuated multiple Ang II-induced stress responses.
DRD1 overexpression increased PI3K/Akt phosphorylation, and PI3K/Akt signaling contributed partly to DRD1's protective effects.
Whether DRD1 causally regulates AF susceptibility in vivo remains to be established.
This research suggests that a protein called dopamine receptor D1 (DRD1) — best known for its role in the brain — may also play a role in the heart during atrial fibrillation (AF), a common and potentially dangerous irregular heart rhythm. By analyzing gene expression data from human heart and fat tissue surrounding the heart, as well as from a mouse model of AF, the researchers found that DRD1 levels were lower in AF-affected tissues compared to healthy tissues. In mice treated with a hormone called angiotensin II, which is known to promote heart stress and arrhythmias, DRD1 was also reduced and the mice showed greater susceptibility to AF. To understand what DRD1 might be doing, the researchers ran experiments in heart muscle cells grown in a lab dish. When they artificially increased DRD1 levels before exposing the cells to angiotensin II stress, the cells fared much better — they showed less cell death, less inflammation, less oxidative damage, and less abnormal cell enlargement (a process called hypertrophy). Part of this protection appeared to work through a well-known cell survival pathway called PI3K/Akt, since blocking this pathway with a drug called LY294002 partially reversed DRD1's protective effects. This research suggests that DRD1 may help protect heart muscle cells from the kinds of stress that contribute to AF, potentially through the PI3K/Akt signaling pathway. However, the study was conducted primarily in cell cultures and mouse models, and the authors caution that it is still unknown whether DRD1 directly causes or prevents AF in living animals. Further research is needed before any conclusions can be drawn about whether targeting DRD1 could be a useful strategy for treating or preventing AF in humans.
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. https://doi.org/10.1007/s11033-026-12755-1