Hypercoagulability and vascular proinflammatory activation promote cardiac-cerebral fibrinogenesis in a rodent model of Chagas disease
Year: 2026
Type: article
Abstract: Cardiomyopathy and stroke are major complications of Chagas disease (CD). We investigated if hypercoagulability, endothelial cell (EC) dysfunction, and blood stasis cause cardiac-cerebral fibrinogenesis in CD. C57BL/6 mice infected with Trypanosoma cruzi (Tc) were evaluated at acute (AT), indeterminate (IT) and chronic (CT) stages of CD. Mice were given anti-parasite, bicistronic immunogens (BCV or BCVR) to determine the role of Tc in fibrinogenesis. We monitored (1) platelet and coagulation cascade activation; (2) cardiac-cerebral blood vessels injury; (3) proinflammatory/prothrombotic phenotypes of microglia, macrophages, and vascular cells; and (4) fibrinogenesis. After quiescent acute phase, plasma levels of coagulation and other factors of platelet activation/aggregation, hypercoagulability, and clotting capacity were increased in IT-CT mice. Proinflammatory and prothrombotic cytokines/chemokines in cardiac-cerebral blood vessels were also significantly increased in IT-CT mice. Loss of cardiac EC and a marked increase in their proinflammatory/cell adhesion response was not compensated by pro-angiogenic/wound-healing response in cardiac-cerebral tissues of infected mice. Microglial proinflammatory activation preceded the vascular inflammation suggesting a feedback cycle of EC activation in brain of infected mice. Treatment with BCV/BCVR controlled the parasite persistence and hypercoagulability/vascular inflammation in infected mice. Importantly, BCV/BCVR treatment abolished the fibrin clots that otherwise were pronounced in heart and brain of IT-CD mice. We conclude that acute Tc infection triggered a subdued hemodynamic disorder, and persistence of low-grade parasites contributed to cardiovascular/cerebrovascular proinflammatory and prothrombotic response and fibrin deposition in mice. BCV/BCVR offer potential immunotherapies for reducing the recurrent clot formation and risk of stroke in CD.Commonly used abbreviations AT, IT, and CT: Acute, intermediate, and chronic stages of T. cruzi infection, respectively; APTT: Activated partial thromboplastin time; BCV: Bicistronic immunogen; BCVR: BCV adjuvanted with RIG-I agonist; CD: Chagas disease; EC: Endothelial cells; INR: International normalized ratio; LV: Left ventricle; PT: Prothrombin time; SMC: Smooth muscle cell; TF: Tissue factor; Tc: Trypanosoma cruzi; uPA: Urokinase plasminogen activator; VCAM1: Vascular Cell adhesion molecule 1; VEGF: Vascular endothelial growth factor.
Source: Emerging Microbes & Infections
Authors: Subhadip Choudhuri, Nisha Jain Garg
Institution: The University of Texas Medical Branch at Galveston
Language: English
Subfield: Epidemiology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,643
OpenAlex ID: W7128631097