Abstract 17299: Extracellular Annexin A2 Promotes Trypanosoma cruzi Cardiotropism
Introduction: Chagas heart disease, caused by infection with Trypanosoma cruzi, is a leading cause of heart failure in the Western Hemisphere. T. cruzi has a propensity to infect the heart, causing a progressive inflammatory cardiomyopathy, yet the basis for cardiac-specific disease remains unclear. In an attempt to understand tissue targeting, we isolated proteins at the cardiomyocyte-T. cruzi interface, revealing a novel interaction between annexins and T. cruzi trypomastigotes.
Hypothesis: We hypothesized that extracellular annexin A2 interactions contribute to association with T. cruzi.
Methods: Isolated membranes from murine cardiomyocytes were labeled, solubilized, and incubated with parasites as the affinity reagent. Membrane proteins that associate with parasites were pulled down and identified by mass spectrometry, revealing annexin A2 as a major component. The contribution of the annexin-parasite interaction during infection was tested through annexin A2 antibody blockade in our primary cell in vitro association model. Two-way ANOVA with Bonferroni correction was applied to test significance.
Results: Antibody blockade significantly reduced parasite association by ~50% in primary myogenic cells, specifically cultured adult cardiomyocytes and skeletal myoblasts, without a reduction in cardiac or skeletal fibroblast association.
Conclusions: Our data demonstrate a novel and relevant interaction between T. cruzi and extracellular membrane-associated annexin A2 in murine cardiomyocytes and skeletal myoblasts. While annexin A2 has a broad tissue distribution, the enrichment in myogenic cells may support differential tissue targeting. Interestingly, other medically important pathogens utilize annexin A2 to associate with target cells. This annexin A2 interaction may be upstream of a known interaction between parasites and the LDL receptor, linked through the action of PCSK9. Understanding the molecular basis underlying tropism may inform novel therapeutic targets to interrupt cellular targeting by T. cruzi.
Author Disclosures: C.L. Epting: Consultant/Advisory Board; Modest; Vivacelle Bio, Inc.. M.F. Alqahtani: None. N.Y. Du: None. D.P. Sullivan: None. D.M. Engman: None.
- © 2014 by American Heart Association, Inc.