Akt/PI3K signaling sustains the chronic alcoholic effects on the heart (862.6)

Abstract

Cardiovascular diseases are the leading causes of increased mortality and morbidity rates. Specifically, alcohol induced cardiomyopathy is a preventable dysfunction that is associated with premature deaths. High alcohol (HA) intake has been shown to negatively impact the heart function into having reduced contractility with dilated cardiomyopathy. However, low alcohol (LA) intake has been clinically shown to be beneficial. Prior studies in our lab have linked the Akt/PI3K pathway to cardiac dysfunction. In this study, we investigate the role of Akt activity (western blot) that contributes to changes in cardiac contraction and calcium mobilization (Ionoptix), cell survival (Cell Viability Assay), caspase activity (caspase 3/7 assay) and oxidative stress associated with chronic LA (0.02%) and HA (0.45%) consumption using Lieber‐DeCarli alcohol diet (4 months). Our results demonstrate that rats on a LA liquid diet experienced decreased caspase activity and increased calcium mobilization and cellular/sarcomere contraction. However, the above Akt‐mediated effects are diminished with rats on a HA diet. Our results also show that the inhibition of NFkB causes further aggravation of alcohol‐induced cardiomyopathy. Our data suggests that Akt signaling plays an important role in supporting the beneficial effects of LA which is diminished with HA exposure having detrimental effects on cardiac function.Grant Funding Source: This work was supported in part by grants NIH/NIAAA/1R15AAA019816‐01A1, and 2G12 RR003048 RCMI/NCRR/