Loss of Adult Cardiac Myocyte GSK-3 Leads to Mitotic Catastrophe Resulting in Fatal Dilated Cardiomyopathy.

ABSTRACT:

Rationale

Cardiac myocyte-specific deletion of either glycogen synthase kinase (GSK)-3α and GSK-3β leads to cardiac protection after myocardial infarction, suggesting that deletion of both isoforms may provide synergistic protection. This is an important consideration because of the fact that all GSK-3-targeted drugs, including the drugs already in clinical trial target both isoforms of GSK-3, and none are isoform specific.

Objective

To identify the consequences of combined deletion of cardiac myocyte GSK-3α and GSK-3β in heart function.

Methods and results

We generated tamoxifen-inducible cardiac myocyte-specific mice lacking both GSK-3 isoforms (double knockout). We unexpectedly found that cardiac myocyte GSK-3 is essential for cardiac homeostasis and overall surviv

SUBMITTER: Zhou J 

PROVIDER: S-EPMC4843504 | biostudies-literature | 2016 Apr

REPOSITORIES: biostudies-literature