Pericyte-derived extracellular vesicles improve vascular barrier function in sepsis via the Angpt1/PI3K/AKT pathway and pericyte recruitment: an in vivo and in vitro study.
Summary
Pericyte-derived EVs carrying Angpt1 enhanced endothelial barrier integrity, proliferation, and angiogenesis in CLP-induced sepsis, reduced systemic inflammatory cytokines, and recruited pericytes. Loss of Angpt1 blunted these benefits by diminishing PI3K/AKT signaling, identifying a mechanistic axis for EV-based vascular therapy.
Key Findings
- PCEVs improved vascular permeability, proliferation, and angiogenesis in CLP-induced gut barrier injury in vivo and in vitro.
- PCEVs reduced serum inflammatory cytokines and promoted pericyte recruitment, protecting intestinal barrier function.
- Angpt1 carried by PCEVs activated PI3K/AKT; Angpt1 knockdown abrogated protective effects by reducing PI3K/AKT activation.
Clinical Implications
EV-based biologics that enhance Angpt1 signaling may restore endothelial and gut barrier function in sepsis, offering an adjuvant strategy to reduce capillary leak and organ dysfunction.
Why It Matters
Defines Angpt1/PI3K/AKT as a tractable pathway by which pericyte EVs repair sepsis-induced barrier failure, advancing EV-based therapeutics for vascular dysfunction.
Limitations
- Preclinical models; absence of dose–response and pharmacokinetic/toxicology data for translational planning
- EV heterogeneity and manufacturing scalability not addressed
Future Directions
Define EV dosing, biodistribution, and safety; test Angpt1-enriched EVs in large-animal sepsis models and explore combination with standard care.
Study Information
- Study Type
- Basic/Mechanistic research
- Research Domain
- Treatment
- Evidence Level
- V - Preclinical in vivo CLP models and in vitro endothelial assays with mechanistic manipulation
- Study Design
- OTHER