Inactivation of AXL in Cardiac Fibroblasts Alleviates Right Ventricular Remodeling in Pulmonary Hypertension.

ABSTRACT: Right ventricular (RV) adaptation critically determines survival in pulmonary hypertension (PH). Since cardiac fibroblasts (FBs) are crucial mediators of cardiac fibrosis, we aim to uncover the mechanism underlying their activation during RV remodeling. Using single-nucleus RNA sequencing (snRNA-seq) across three rodent PH models-hypobaric hypoxia and Sugen 5416/hypoxia in mice, and monocrotaline in rats-we identified elevated Axl expression in RV FBs under PH. AXL upregulation was consistently observed in RV FBs from both human PH patients and animal models. Cardiac FB-specific Axl overexpression exacerbated RV remodeling in both PH and pulmonary artery banding (PAB) models, whereas Axl knockdown in FBs alleviated this remodeling. Functionally, AXL promoted FB proliferation, migration, an

SUBMITTER: Wu LW 

PROVIDER: S-EPMC12903973 | biostudies-literature | 2026 Feb

REPOSITORIES: biostudies-literature