Abstract 3924: Cardiomyocyte-Specific Silencing of PTEN Limits Myocardial Ischemia-Reperfusion Injury in vivo
Background: Phosphoinositide 3-kinase (PI3K) mediates signal transduction through phosphorylation of phosphatidylinositol (PtdIns) to produce PtdIns (3,4,5)P3, while lipid phosphatase and tensin homolog on chromosome ten (PTEN) antagonize PI3K activity by dephosphorylating PtdIns(3,4,5)P3. PI3K mediates cell survival, whereas PTEN negates this effect.
Purpose: To determine whether silencing PTEN using a mouse model with cardiomyocyte-specific and tamoxifen (Tam)-iducible inactivation of PTEN affect myocardial infarct size in vivo.
Methods: Cardiac specific inducible PTEN knockout (PTENCKO) mice were generated by crossing αMHC-Cre-Mer-Cre mice to PTENFLOX/FLOX mice. PTEN deletion was achived after 7d of i.p. tamoxifen (20 mg/kg/d) administration. PTENFLOX/FLOX mice treated with or without Tam served as controls. Mice were anesthetized with ketamine and xylazine and underwent 30min coronary artery occlusion followed by 4h reperfusion. Area at risk (AR) was assessed by blue dye and infarct size (IS) by TTC. Effective silencing of PTEN in cardiomyocytes was verified by immunohistochemistry and immunofluorescence.
Results: Body weight and the size of AR were comparable among the three groups (Table⇓). IS (% of AR) was significantly smaller in the PTENCKO mice than in the PTENFLOX/FLOX mice. Tam had no effect on IS in the PTENFLOX/FLOX mice.
Conclusions: Cardiomyocyte-specific silencing PTEN limits IS.