Increased metallopeptidase activity, compromised endothelial integrity and impaired pathogen recognition revealed by transcriptomics in Angiostrongylus vasorum-infected dogs with hypocoagulability and vascular dysfunction

Dogs infected with the cardiopulmonary nematode Angiostrongylus vasorum are at high risk to die because of the associated bleeding pathologies, which remain poorly understood. Given their central role in immune surveillance and signaling, we analyzed transcriptomic profiles from (i) A. vasorum -infected dogs presenting with hypocoagulability (Inf hypo ; n = 5), (ii) infected dogs with normal coagulation values (Inf norm ; n = 5), and (iii) uninfected controls (UC; n = 12). Alongside classical hematology and coagulation parameters, including rotational thromboelastometry, we generated a global transcriptomic profile of circulating blood cells, enabling the identification of differentially expressed genes following infection. Fibrinogen levels were significantly lower in Inf hypo than in Inf norm . All Inf hypo dogs showed out-of-range prothrombin times. Matrix metalloprotease transcripts were strongly upregulated among infected dogs, regardless of their coagulation status, which might amplify vascular disruption and inflammation. Analysis of downregulated transcripts in infected dogs compared to UC indicated a loss of endothelial integrity, especially at the level of the lungs, and of inflammatory processes contributing to fibrinolysis and coagulopathies. Endothelial injury is a known trigger of disseminated intravascular coagulation and consumption of coagulation factors, which could explain the observed coagulation disorders induced by A. vasorum infection. The multifaceted alterations observed in hematologic and coagulation parameters, ROTEM, and transcriptomic profiles of A. vasorum -infected dogs point to a dynamic and evolving disruption of hemostatic balance. While some animals show signs of early compensatory hypercoagulability, others seem to progress toward a state consistent with DIC, marked by factor consumption, endothelial dysfunction, and impaired fibrinogen-dependent clotting. • Angiostrongylus vasorum is a potentially lethal cardiopulmonary nematode of dogs. • We conducted a global blood transcriptomics analysis in A. vasorum -infected dogs. • Hypocoagulable dogs showed low fibrinogen and altered prothrombin times. • Upregulated metalloproteinases are associated with vascular damage and inflammation. • Data suggest coagulopathy progressing from compensation to fibrinolysis and disseminated intravascular coagulation.