IBIMOL   23987
INSTITUTO DE BIOQUIMICA Y MEDICINA MOLECULAR PROFESOR ALBERTO BOVERIS
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Unravelling the relationship between the severity of endotoxemia with mitochondria dysfunction: impact in cardiac function.
Autor/es:
VICO, TAMARA; LORENZETTI, MARIO; GINART, SANTIAGO; DANNUNZIO, VERÓNICA; ALVAREZ, SILVIA; MARCHINI, TIMOTEO; FERRERO, MARIANA; MAZO, TAMARA; EVELSON, PABLO; VANASCO, VIRGINIA; ADÁN AREÁN, JUAN SANTIAGO; CORACH, DANIEL; GELPI, RICARDO
Lugar:
Buenos Aires
Reunión:
Simposio; Frontiers in Bioscience 3; 2018
Institución organizadora:
Instituto de Investigación en Biomedicina de Buenos Aires (IBioBA, CONICET ? Instituto Partner de la Sociedad Max Planck)
Resumen:
Mitochondrial dysfunction involves impairment of O2 consumption and ATP production, leading to cell bioenergetics impairment. Sepsis and endotoxemia, as a host dysregulated response to infection, induces organ failure with high mortality rate worldwide, particularly affecting the heart. In this work, the relationship between cardiac mitochondrial function and the magnitude of the inflammation response, emphasising in the impact in heart function is elucidated. An experimental model of severe endotoxemia (septic conditions; ip injection 8 mg kg-1 body weight) or low-grade endotoxemia (metabolic endotoxemia; ip injection 0.5 mg kg-1 body weight) were used, and cardiac mitochondrial function was analysed as well as systemic pro-inflammatory cytokines and NO, and heart contractile state. Our results showed that mitochondrial ATP production, O2 consumption and mitochondrial inner membrane potential decreases are related to blood NO and TNF-α levels, as well as mRNA transcript of cardiac cytokines in endotoxemia. Cardiac relaxation is altered only in severe endotoxemia, although both contractile and lusitropic reserve were found impaired in both treatments in response of work-overload. These results indicate that correct performance of the heart depends on mitochondrial function not only in septic conditions, but also in metabolic endotoxemia. Target therapies directed to restore mitochondria function in these inflammatory scenarios would be a novel strategy to overcome cardiac failure.