Proteomic Analysis of Endothelial Activation Induced by Adult Angiostrongylus vasorum Homogenate: Insights into Vascular Remodeling and Hemostatic Imbalance

The interaction between Angiostrongylus vasorum and the vascular endothelium of the host plays a key role in the pathogenesis of canine angiostrongylosis. The adult stage of A. vasorum resides in right ventricles and pulmonary arteries of dogs and foxes and maintains close contact with the endothelium, whose activation may contribute to the hemostatic and hemorrhagic disorders observed in infected animals. However, the molecular mechanisms underlying this endothelial dysfunction remain poorly understood. To investigate this interaction, an in vitro model of vascular endothelial cells was stimulated with the adult A. vasorum homogenate. Quantitative proteomic analysis, combined with bioinformatic tools, identified 691 and 6011 protein groups in the cell supernatants and the cell lysates, respectively. Of these, 213 proteins in the cell supernatants (193 up-regulated and 20 down-regulated) and 564 in the cell lysates (358 up-regulated and 206 down-regulated) showed differential expression compared to control cells. Up-regulated proteins included TFPI, CD59, VWF, ANGPT2, MMRN1, and FLT1, which are involved in endothelial activation, angio-genesis, and coagulation regulation. Conversely, C3, SERPINE1, SERPINB2, PLAU, PLAUR, and ICAM1 were down-regulated, suggesting modulation of fibrinolysis, inflammation, and cell adhesion pathways. These findings indicate that adult A. vasorum homogenate induces a multifactorial endothelial activation characterized by dysregulation of coagulation, complement, and vascular remodelling pathways. Future studies focusing on the temporal and molecular characterization of endothelial responses to excretory/ secretory antigens in both definitive and accidental hosts will further clarify the mechanisms of vascular pathology and parasite tolerance.