Pulmonary vascular disease & thromboembolism
Endothelial SHMT2 Drives Pulmonary Vascular Remodeling Through Noncanonical Pathway in Pulmonary Hypertension
Authors' conclusion
This study highlights endothelial SHMT2 as an important contributor to PH pathogenesis and reveals a noncanonical SHMT2-RhoB pathway that promotes endothelial dysfunction.
Study context
- Population
- Patients with pulmonary hypertension (PH) (lung samples) and rodent PH models (hypoxia-exposed mice; monocrotaline- or Sugen 5416/hypoxia-induced rats)
Methodological detailshuman lung samples, rodent PH models, endothelial cell-specific conditional knockout, AAV9-mediated gene modulation, virtual screening
- Human lung samples
- Rodent PH models
- Endothelial cell-specific conditional knockout
- AAV9-mediated gene modulation
- Virtual screening
Main finding
As reported in the abstract
- SHMT2 upregulated predominantly in pulmonary vascular endothelium of patients with PH and multiple rodent PH models
- Endothelial Shmt2 deletion markedly attenuated pulmonary vascular remodeling and RV dysfunction in PH mice; endothelial Shmt2 overexpression aggravated PH
- AAV9-mediated endothelial Shmt2 knockdown alleviated PH phenotypes in rat models
- SHMT2 promoted hypoxia-induced endothelial barrier dysfunction mainly through a noncanonical function, blocking K63-ubiquitin-mediated lysosomal degradation of RhoB
- Namodenoson identified by virtual screening as SHMT2-RhoB pathway inhibitor; showed preventive and therapeutic effects against PH in vivo
Original publication
Endothelial SHMT2 Drives Pulmonary Vascular Remodeling Through Noncanonical Pathway in Pulmonary Hypertension. Circulation. Published 10 June 2026. doi:10.
Summarised from the published abstract; every number is checked against it