IBIMOL   23987
INSTITUTO DE BIOQUIMICA Y MEDICINA MOLECULAR PROFESOR ALBERTO BOVERIS
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Differences in the protection mechanisms of preconditioning and postconditioning induced by vagal stimulation in myocardial infarction in mice
Autor/es:
KELLY J; BERNATENÉ M; DOMINICI FP; MUÑOZ M; GONZÁLEZ MAGLIO D; BUCHHOLZ B; MÉNDEZ DIODATI N; GELPI RJ
Lugar:
Mar del Plata
Reunión:
Congreso; LXI Reunión Anual de la Sociedad Argentina de Investigación Clínica (SAIC); 2016
Institución organizadora:
Sociedad Argentina de Investigación Clínica
Resumen:
We have previously proven that vagal stimulation (VS) decreases infarct size both when applied before ischemia and during reperfusion. However, theirmechanisms are yet unknown. Thus, our objective was to study the molecular pathways involved in the protection of preischemic VS (pVS) and reperfusion VS (rVS). Mice were randomly assigned to the following groups: Sham (n=6); 30 min of regional myocardial ischemia and 15 min of reperfusion without VS (I/R, n=6); with 10 min of pVS with (n=6) and without (n=6) muscarinic blockade with atropine; 10 min of rVS with (n=6) and without (n=6) alpha-7 nicotinic blockade with MLA. Left ventricle samples were taken for Western blotting at the end of reperfusion. IL-6 levels were assessed by ELISA in myocardium and plasma after 2 h of reperfusion. pVS increased Akt phosphorylation in comparison to the I/Rand Sham group (4.2±0.64; 2.15±0.17 and 0.80±0.13 respectively). This was reversed with administration of atropine (1.13±0.34). GSK-3β had a similar increase (4.65±0.52; 2.91±0.36 and 1.05±0.05; respectively) and reversed as well with atropine (1.44±0.33). There were no significant differences in ERK1/2, JAK2 and STAT3 phosphorylation. rVS produced a non significant rise in JAK2 phosphorylation compared to I/R (2.36±0.40 and 1.64±0.2; respectively). There were no significant differences between I/R, rVS and rVS+MLA groups in Akt,GSK-3β, ERK1/2 and STAT3 phosphorylation. Additionally, rVS did not reverse the increase in IL-6 produced during ischemia/reperfusion. In conclusion, pVS reduces infarct size in mice by muscarinic activation of the Akt/GSK-3β pathway. Conversely, rVS protection seems to be mediated by alpha-7 nicotinic activation of the JAK2 pathway, independently of local myocardial and systemic anti-inflammatory responses.