Pulmonary vascular disease & thromboembolism
NMDA-Type Glutamate Receptor Activation Promotes Vascular Remodeling and Pulmonary Arterial Hypertension
Authors' conclusion
These results reveal a dysregulation of the glutamate-NMDAR axis in the pulmonary arteries of patients with PAH and identify vascular NMDARs as targets for antiremodeling treatments in PAH.
Study context
- Population
- Patients with pulmonary arterial hypertension (PAH) and controls; human pulmonary arterial smooth muscle cells; mouse and rat models of pulmonary hypertension
Methodological detailshuman tissue, cell culture, smooth muscle-specific N-methyl-d-aspartate receptor (NMDAR) knockout mice (chronic hypoxia), monocrotaline rat model
- Human tissue
- Cell culture
- Smooth muscle-specific NMDAR knockout mice (chronic hypoxia)
- Monocrotaline rat model
Main finding
As reported in the abstract
- Glutamate accumulation, NMDAR upregulation and increased GluN1-subunit phosphorylation in pulmonary arteries of patients with PAH
- Kv channel inhibition and endothelin type A receptor activation amplified calcium-dependent glutamate release from human pulmonary arterial smooth muscle cells; endothelin type A and PDGF receptor activation led to NMDAR engagement
- PDGF-BB-induced proliferation of human pulmonary arterial smooth muscle cells involved NMDAR activation
- Smooth-muscle NMDAR deficiency in mice attenuated hypoxia-triggered vascular remodeling
- NMDAR blockade in monocrotaline rats improved cardiac and vascular remodeling, decreasing endothelial dysfunction, cell proliferation and apoptosis resistance
Original publication
NMDA-Type Glutamate Receptor Activation Promotes Vascular Remodeling and Pulmonary Arterial Hypertension. Circulation. Published 14 February 2018. doi:10.
Summarised from the published abstract; every number is checked against it