The Oxidized Phospholipid PGPC Impairs Angiogenesis by Inhibiting Endothelial Autophagosomal–Lysosomal Fusion Through NPC1-Induced Syntaxin 17 Acetylation and Ubiquitination
Authors' conclusion
PGPC promotes the acetylation and subsequent ubiquitin-mediated degradation of STX17 by increasing NPC1, leading to a reduction in the level of STX17 associated with VAMP8, which inhibits autophagosomal-lysosomal fusion and angiogenesis. Targeting PGPC, NPC1, or STX17 may represent novel therapeutic approaches to promote angiogenesis in patients with CAD.
Study context
- Population
- Patients with coronary artery disease (CAD) (plasma PGPC); cultured endothelial cells; C57BL/6J mice
- Comparison
- Effects of PGPC on angiogenesis and autophagy
Methodological detailssubcutaneous Matrigel plug assay, hindlimb ischemia model, myocardial infarction model
- Subcutaneous Matrigel plug assay
- Hindlimb ischemia model
- Myocardial infarction model
Main finding
As reported in the abstract
Plasma PGPC in CAD
- Plasma PGPC levels increased in patients with CAD, positively correlated with CAD severity and negatively correlated with coronary collateral artery formation
Further findings
Angiogenesis in vitro and in vivo
- PGPC inhibited endothelial cell migration and tube formation
- PGPC suppressed neovascularization in Matrigel plugs and reduced blood flow recovery in hindlimb ischemia
- PGPC attenuated angiogenesis in the ischemic myocardium after myocardial infarction
- VEGFA-induced proangiogenic effects in ischemic hearts significantly inhibited by PGPC
Mechanism
- PGPC inhibited STX17 expression by promoting its acetylation and subsequent ubiquitination and degradation
- PGPC upregulated NPC1 through CD36
- NPC1 recruited ACAT1 to promote STX17 acetylation and degradation, and competed with STX17 to bind VAMP8, inhibiting eNOS, ERK1/2 and nitric oxide production
- E06, STX17 overexpression, or silencing of NPC1 reversed the inhibitory effect of PGPC on angiogenesis by restoring autophagic flux
Original publication
The Oxidized Phospholipid PGPC Impairs Angiogenesis by Inhibiting Endothelial Autophagosomal–Lysosomal Fusion Through NPC1-Induced Syntaxin 17 Acetylation and Ubiquitination. Circulation. Published 6 October 2026. doi:10.
Summarised from the published abstract; every number is checked against it