@article{bibcite_7586,
  keywords = {3D Brain Microvascular Models, AKB-9778, Angiopoietin{\textendash}Tie Axis, Cerebral Malaria, Pericytes},
  author = {Rory K. M. Long and Fran{\c c}ois Korbmacher and Paolo Ronchi and Hannah Fleckenstein and Martin Schorb and Waleed Mirza and Mireia Mallorqu{\'\i} and Ruth Aguilar and Gemma Moncunill and Yannick Schwab and Maria Bernabeu},
  title = {Plasmodium falciparum impairs Ang-1 secretion by pericytes in a 3D brain microvessel model},
  abstract = {Disruption of the vascular protective angiopoietin{\textendash}Tie axis is common in cerebral malaria (CM) patients, who display elevated angiopoietin-2 (Ang-2) and reduced angiopoietin-1 (Ang-1) blood concentrations. The role of pericytes in CM pathogenesis remains unexplored, despite being a major source of brain Ang-1 secretion and evidence of pericyte damage observed in CM postmortem samples. Here, we engineered a human 3D microfluidics-based brain microvessel model containing the minimal cellular components to replicate the angiopoietin{\textendash}Tie axis, human primary brain microvascular endothelial cells, and pericytes. This model replicated pericyte vessel coverage and ultrastructural interactions present in the brain microvasculature. When exposed to P. falciparum-iRBC egress products, 3D brain microvessels presented decreased Ang-1 secretion, increased vascular permeability, and minor ultrastructural changes in pericyte morphology. Notably, P. falciparum-mediated barrier disruption was partially reversed after pre-treatment with recombinant Ang-1 and the Tie-2 activator, AKB-9778. Our approach suggests a novel mechanistic role of pericytes in CM pathogenesis and highlights the potential of therapeutics that target the angiopoietin{\textendash}Tie axis to rapidly counteract vascular dysfunction caused by P. falciparum.},
  year = {2025},
  journal = {EMBO Molecular Medicine},
  volume = {17},
  pages = {3110-3138},
  month = {2025-11-01},
  issn = {1757-4684},
  url = {https://doi.org/10.1038/s44321-025-00319-y},
  doi = {10.1038/s44321-025-00319-y},
  language = {en},
}