Targeted delivery of <i>BMPR2</i> mRNA attenuates pulmonary arterial hypertension by reversing pulmonary vascular remodeling.

ABSTRACT: Disrupted bone morphogenetic protein type 2 receptor (BMPR2) signaling in endothelial cells drives pulmonary arterial hypertension (PAH). However, targeted recovery of this signaling pathway by lipid nanoparticles (LNPs) has not been explored as a therapy. Here, we employed Design of Experiments to optimize the delivery efficiency of LNPs targeting pulmonary endothelial cells developed by our laboratory, resulting in a remarkable 35-fold increase in a simplified three-component formulation without helper lipids. Administration of BMPR2 mRNA LNPs effectively reversed established PAH in two experimental rat models (monocrotaline or SU5416-hypoxia) by reversing pulmonary vascular remodeling. Specifically, BMPR2 mRNA LNPs replenished the expression of BMPR2 protein and subsequent

SUBMITTER: Cao Y 

PROVIDER: S-EPMC12541623 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature