Work

P2X7 receptors promote atrial remodeling and atrial fibrillation susceptibility via reactive oxygen species‐mediated mitogen‐activated protein kinase signaling activation

Year: 2026

Type: article

Abstract: Atrial fibrillation (AF), the most common clinical arrhythmia, is driven by inflammatory activation and oxidative stress, though precise molecular links remain unclear. This study identifies the P2X7 receptor as a key upstream regulator orchestrating proarrhythmic atrial remodeling through reactive oxygen species (ROS)-mediated mitogen-activated protein kinase (MAPK) signaling. Transcriptomic analysis of rapid-paced cardiomyocytes revealed P2X7 upregulation and MAPK pathway enrichment. Functional validation demonstrated that P2X7 activation promotes ROS accumulation, MAPK phosphorylation (p-ERK, p-p38, and p-JNK), and pro-inflammatory cytokine release (IL-6 and IL-1β), culminating in action potential shortening and calcium handling dysfunction. Critically, both P2X7 inhibition (A-438079) and ROS scavenging (NAC) attenuated this signaling axis. In vivo, P2X7 antagonism reduced AF susceptibility, improved conduction heterogeneity, and ameliorated structural and autonomic remodeling. These results establish the P2X7-ROS-MAPK axis as a central mechanism in AF vulnerability and highlight its therapeutic potential.

Source: Journal of Cell Communication and Signaling

DOI: 10.1002/ccs3.70071

Authors: Lingnan Zhang, Yeran Zhu, Xinshun Gu

Institutions: Hebei Medical University, Second Hospital of Hebei Medical University, Affiliated Hospital of Hebei University

Language: English

Topic: Adenosine and Purinergic Signaling

Subfield: Physiology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: hybrid

Estimated APC paid: $2,860