Pulmonary vascular disease & thromboembolism
Endothelial Heterogeneity in the Response to Autophagy Drives Small Vessel Muscularization in Pulmonary Hypertension
Authors' conclusion
Autophagic activation by hypoxia induces in parallel PAEC proliferation and MVEC apoptosis.
Study context
- Population
- Murine, rat and human PAECs and microvascular ECs (MVECs); lung tissue from patients with pulmonary hypertension (PH) and animal models
Main finding
As reported in the abstract
- PAECs proliferated in response to hypoxia, whereas MVECs underwent apoptosis (in vitro and in vivo)
- Single-cell RNA sequencing: hypoxia induced an antiapoptotic, proliferative phenotype in arterial endothelial cell (ECs); capillary ECs showed a propensity for cell death
- Distinct responses prevented in hypoxic Atg7EN-KO mice or after ATG7 silencing, replicated by autophagy stimulation
- In lung tissue from mice, rats or patients with PH, PAEC abundance in precapillary arterioles increased and MVEC abundance reduced vs controls
- EC replacement prevented by genetic or pharmacological autophagy inhibition in vivo
- Conditioned medium from hypoxic PAECs, not MVECs, promoted pulmonary artery smooth muscle cell proliferation and migration, platelet-derived growth factor-dependent
- Autophagy inhibition attenuated PH development and distal vessel muscularization in preclinical models
Original publication
Endothelial Heterogeneity in the Response to Autophagy Drives Small Vessel Muscularization in Pulmonary Hypertension. Circulation. Published 14 June 2024. doi:10.
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