Cardiomyocyte-specific Deletion Of Cdc42 Protects Cardiac Ischemia-reperfusion Injury In Mouse

Background and aimsIschemia-reperfusion(I/R)injury of the heart and cardiac hypertrophy are the two most common heart diseases and eventually lead to heart failure.The detail intracellular signal pathways are still not clear.Cdc42,a small GTPase,a member of the Rho family,has been proved as molecular switches in signal pathways and involved in cellular activity including cell polarization,gene transcription,migration,cytoskeleton formation and cancer cell invasion,etc.The purpose of this study was to investigate the effects of cardiac specific Cdc42 knockout mice on ischemia-reperfusion(I/R)injury of the heart,and to explore the possible molecular mechanisms.Materials and methodsThe cardiac specific deletion of Cdc42 mice(Cdc42flox/flox[Cre])were obtained by crossing Cdc42flox/flox mice and MLC-2C-Cre mice.The mice were viable and maintained as stable breeding.Cardiac ischemia-reperfusion(I/R)injury were induced by perfusing with langendorff system,and analyzed the heart function and injuries by the perfusion flow and the release of LDH from perfused hearts,respectively.Isolated adult cardiomyocytes from the null mice were stimulated by Isoprenaline and Angiotensin II,and the expression of related genes were also examined.ResultsUnder stable perfusion pressure with langendorff system,the redution of perfusion flow and the release of LDH from perfused Cdc42flox/flox[Cre] hearts are significantly less than control group when performing ischemia-reperfusion(I/R).The cardiomyocyte-specific deletion of Cdc42 significantly reduced the expressions of GSK3? and PPP3 CA which were induced by Isoprenaline in cardiac myocytes and further reduced the expression of cardiac transcription factors of GATA4 and Mef2.ConclusionWe have successfully prepared the cardiomyocyte-specific deletion of Cdc42 model mice.Our results revealed that the cardiomyocyte-specific Cdc42 null mice significantly protected the heart from I/R injury and the mechanism might involved in inhibition of Iso-induced increased expressions of GSK-3? and PPP3 CA in heart and furthermore,the expressions of cardiac transcriptors GATA4 and Mef2 were eventually reduced by the deletion of Cdc42 in heart.