Role Of PTEN-PI3k-PDK1-Akt Pathway In Cardiac Development And Function

There are many signaling pathways involved in heart development. Any fault in these signals will result in cardiac abnormal development and congenital heart disease.The phosphatidylinositol 3-kinase (PI3K) signaling pathway, which regulates crucial biological processes including metabolism, survival, proliferation, growth, and migration, is involved in the development progress of heart. The lipid phosphatase PTEN negatively regulates the pathway by lowers the levels of the PI3K product PIP3. PDK1 is required to phosphorylate and activate Akt, a key downstream effector of PI3K signaling, in response to elevated PIP3.There are many studies in the protection role of this pathway in myocardial ischemia and heart remodeling, however, little in the embryonicheart development. Germ-line deletion of some genes involved in this pathway result in embryo lethality, so we generated knockout mice with cardiomyocytes-specific deletion of these genes by Cre-LoxP system To study the function of Akt in cardiac development and function.The aMHC-Cre is to inactivate genes in cardiomyocytes of postnatal mice, and the Mespl-Cre is for the cardiac progenitor cells.We first reported that the phosphorylation of Akt S473 is very important to the activity of Akt, and revealed the role of PTEN-PI3K-PDK1-Akt pathway in cardiac development and function.The data presented here could be helpful to study the etiology and therapy of human congenital heart disease and dilated cardiomyopathy.