Bone morphogenetic protein receptor II regulates pulmonary artery endothelial cell barrier function

Area of Science:

• Cardiovascular Biology
• Immunology
• Pulmonary Medicine

Background:

• Mutations in bone morphogenetic protein receptor II (BMPR-II) are linked to heritable pulmonary arterial hypertension (PAH).
• Not all individuals with BMPR-II mutations develop PAH, suggesting other factors are involved.
• BMPR-II may play a role in regulating inflammatory responses in the pulmonary vasculature.

Purpose of the Study:

• To investigate the role of BMPR-II in maintaining pulmonary artery endothelial barrier function.
• To determine if BMPR-II loss contributes to inflammation and leukocyte infiltration in pulmonary arteries.
• To elucidate the mechanisms by which BMPR-II deficiency may initiate heritable PAH.

Main Methods:

• Utilized static- and flow-based in vitro systems to assess endothelial barrier function.
• Examined leukocyte transmigration across pulmonary artery endothelial monolayers.
• Employed a murine model with endothelial BMPR-II loss and in vitro stimulation with TNF-α and TGF-β1.

Main Results:

• BMPR-II maintains pulmonary artery endothelial barrier function by suppressing leukocyte transmigration.
• Loss of endothelial BMPR-II in vitro and in vivo increased leukocyte extravasation.
• Enhanced leukocyte transmigration was dependent on CXCR2 signaling following inflammatory stimulation.

Conclusions:

• Loss of BMPR-II in pulmonary vascular endothelium compromises barrier integrity.
• This compromised barrier promotes leukocyte extravasation, contributing to inflammation.
• BMPR-II deficiency may be a critical factor in initiating heritable PAH by increasing susceptibility to inflammation.