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

## TL;DR

This study explores how the parasite Angiostrongylus vasorum activates dog endothelial cells, causing vascular and coagulation issues.

## Contribution

The study identifies specific proteins dysregulated by the parasite's homogenate, revealing molecular mechanisms of endothelial dysfunction.

## Key findings

- Adult A. vasorum homogenate induces endothelial activation through dysregulation of coagulation and vascular remodeling proteins.
- Up-regulated proteins include TFPI, CD59, and VWF, while down-regulated proteins include C3 and SERPINE1.
- The findings suggest a multifactorial endothelial response involving inflammation, fibrinolysis, and cell adhesion pathways.

## Abstract

The parasite Angiostrongylus vasorum damages the vascular endothelium in dogs, leading to severe coagulation and hemorrhagic disorders. Proteomic analysis shows that its antigens trigger endothelial activation, dysregulating proteins involved in inflammation and vascular remodeling. These findings clarify the molecular mechanisms behind the vascular pathology and provide a clearer understanding of how the parasite interacts with and compromises the host’s system.

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.