Neuroendocrine activation in the pathophysiology of Chagas cardiomyopathy

Jose A. Rumbo-Romero, Institute of International Health, Charité – Universitätsmedizin Berlin, Berlin, Germany
Hilda Rangel-Flores, Investigation Centre for Population Health, Instituto Nacional de Salud Pública, Cuernavaca, Mor., Mexico
Celso Ramos, Centre for Infectious Disease Research, Instituto Nacional de Salud Pública, Cuernavaca, Mor., Mexico
Ernesto Gutiérrez-Perucho, Unit for Clinical Cardiologic Investigation, Iguala, Gro., Mexico

Chagas disease is a zoonosis affecting 6 million people across 21 countries in Central and South America. Chronic Chagas cardiomyopathy represents the most severe form of organ involvement in the disease, characterized by a high incidence of arrhythmias, stroke, thromboembolic events, heart failure, and sudden cardiac death. Decades of research have focused on persistent parasitism, parasite-induced autoimmune processes, and inflammatory responses to Trypanosoma cruzi as potential mechanisms contributing to the degeneration of cardiac myofibers. In recent years, neuroendocrine imbalances involving the sympathetic nervous system, the hypothalamic-pituitary-adrenal axis, and central T-cell tolerance in the thymus have been proposed as significant contributors to the pathophysiology. The roles of pituitary hormones, the pineal hormone, adipose tissue, and testosterone have also been emphasized. Thymic atrophy, mediated through caspase-dependent mechanisms, along with the aberrant migration of immature and autoreactive T cells into peripheral lymphoid tissues and the myocardium, are central features that likely act concurrently or synergistically with the already known mechanisms to drive the progression of the disease to its advanced stages. mecanismos dependientes de caspasas, junto con la migración aberrante de células T inmaduras y autorreactivas hacia los tejidos linfoides periféricos y el miocardio, constituye un conjunto de procesos que probablemente actúan de forma concurrente o sinérgica con los mecanismos ya conocidos, impulsando así la progresión de la enfermedad hacia sus etapas avanzadas.

Keywords: Chagas cardiomyopathy. Neurosecretory systems. Endocrine system. Nervous system. Pathophysiology.