Trypanosoma cruzi infection-induced changes in cardiac microvascular endothelial cell morphology and function

<b>Introduction.</b> Six to seven million individuals are infected with <i>Trypanosoma cruzi</i>, the causative agent of Chagas disease. With 12,000 deaths annually, chronic Chagas disease remains a significant global health challenge due to persistent vector transmission, increasing non-vector transmission and limited therapeutic options. Chronic Chagas cardiomyopathy is a leading cause of morbidity and mortality, yet the underlying mechanisms remain poorly understood.<b>Gap Statement.</b> Since its initial description more than 100 years ago, research efforts into the cardiomyopathy found in chronic Chagas disease have primarily focused on the contributions of immune cells, cardiomyocytes and cardiac fibroblasts, leaving a significant gap in understanding the role of microvascular endothelial dysfunction in disease progression.<b>Aim.</b> The aim of this study was to identify any morphological or functional changes to cardiac microvascular endothelial cells induced by <i>T. cruzi</i> infection with the potential to contribute to the pathologies found in chronic Chagas disease.<b>Methodology.</b> We cultured primary cardiac microvascular endothelial cell monolayers <i>in vitro</i> and infected them with <i>T. cruzi</i> trypomastigotes or exposed them to conditioned media collected from control or infected endothelial cells. Cells were analysed for changes in morphology and proliferation, by wound healing assays for measurements of migratory capacity and by tube-forming assay to characterize their ability to form capillary-like structures.<b>Results.</b> We show that <i>T. cruzi</i> infection leads to the development of hypertrophic multinuclear cells, inhibits endothelial proliferation, increases endothelial migration and results in changes in several aspects of angiogenesis.<b>Conclusion.</b> We present data to demonstrate morphological and functional changes in cardiac endothelial cells that occur as a result of <i>T. cruzi</i> infection and propose that these changes may contribute to endothelial dysfunction and the development of chronic Chagas cardiomyopathy.