Masahiro Nishihara

Impairment of cardioprotective PI3K-Aktsignaling by post-infarct ventricularremodeling is compensated by anERK-mediated pathway

AbstractRecently we found that post-infarct remodeling disrupts PI3KAkt signaling triggered by erythropoietin (EPO) but an unknown compensatory mechanism preserves EPO-induced protection against infarction in those hearts. In this study, we examined the possibility that ERK-mediated signaling is the compensatory mechanism affording protection in post-infarct remodeled hearts. Four weeks after coronary ligation in situ (post-MI group, post-MI) or a sham operation (sham group, Sham), hearts were isolated, perfused and subjected to 25-min global ischemia/2-h reperfusion. Infarct size was expressed as a percentage of risk area size (%I/R), from which scarred infarct by coronary ligation was excluded. EPO infusion (5 U/ml) before ischemia reduced %I/R similarly in Sham and post-MI (from 62.0 ± 5.1 to 39.4 ± 4.8 in Sham and from 58.6 ± 6.6 to 36.3 ± 3.8 in post-MI). PD98059, a MEK1/2 inhibitor, abolished this EPO-induced protection in post-MI (%I/R = 60.7 ± 4.9) but not in Sham (%I/R = 35.1 ± 5.4). EPO induced PI3Kdependent phosphorylation of Akt in Sham but not in post-MI. EPO increased phosphorylation levels of ERK1/2 both in Sham and post-MI, but this phosphorylation was diminished by a PI3K inhibitor in Sham but not in post-MI. These results suggest that PI3K-independent activation of ERK compensates the lack of signal input from the PI3K-Akt pathway to achieve EPO-induced protection in the remodeled myocardium.

Atrial electromechanical interval may predict cardioembolic stroke in apparently low risk elderly patients with paroxysmal atrial fibrillation.

A considerable number of patients with atrial fibrillation (AF) develop cardioembolic stroke (CE) despite low CHADS2 score. We examined the possibility that use of the atrial electromechanical interval (AEMI) improves prediction of CE in patients with paroxysmal AF (PAF), particularly those with low CHADS2 score.