HIF-1Α/PURINERGIC AXIS IS ALTERED IN PATIENTS WITH CHRONIC CHAGAS DISEASE

SANMARCO LM; MINGUEZ, A; BERGERO G; EBERHARDT N; VIGLIANO CA; VISCONTI, LM; AOKI P

Mar del Plata

Congreso; Reunión Anual Sociedad Argentina de Investigación Clínica; 2018

Sociedad Argentina de Investigación Clínica

Introduction: The molecular mechanisms involved in the development of human chronic Chagas cardiomyopathy (CCC) are still largely unknown. Purinergic system components have taken a robust significance as danger signals and modulators of immunity. Ischemic cells release ATP (inflammasome activator), which is metabolized by CD39/CD73 ectoenzymes toanti-inflammatory adenosine. We have reported that CD73 pharmacological inhibition during acute T. cruzi murine infection reduced progression of CCC. The aim of this study was to explore the hypoxia-inducible factor-1α (HIF-1α)/purinergic systemaxis in immune cells from infected individualsand in cardiac explants from CCCpatients.Materials and Methods:Seropositive patients (n= 24)wereevaluated clinically and by electrocardiogram and chest X-ray. The uninfected control group (n= 24) consisted of age-matched individuals. Cardiac tissue samples from end-stage CCC patients were stained by IHC/IF. The myocarditis degree was determined considering the number of CD68+ plusCD3+ cells,as follow: Severe≥median number; Moderate 25-50th percentile; or Mild≤25th percentile.Results: In comparison with control donors, infected patients showed higher frequency of HIF-1á+ and IL-1β+ circulating monocytes with increased nitric oxide production (p