The Role Of PTEN In Cardiac Regeneration And Protection From Myocardial Infarction

Background The world’s highest rate of death is from cardiovascular disease.According to epidemiological statistics,from 1990 to 2017,about 9 million people worldwide died of ischemic heart disease.According to the National Cardiovascular Center,the prevalence of cardiovascular disease in China is still rising,and the number of patients in 2017 has reached 290 million.Myocardial infarction(MI)is a major type of cardiovascular disease.Because lack of blood supply,a lot of cardiomyocytes in the heart undergo irreversible death,which seriously affects heart function and finally lead to heart failure.At present,the clinical methods for treating MI are physical methods,but it is unable to repair damaged cardiomyocytes.The scar tissue formed by death of cardiomyocytes cannot be removed.If combine physical and biological methods to promote myocardial proliferation,there will be beneficial to improve the survival rate of the MI patient.The adult mammalian cardiomyocytes exit cell cycle,most of them no longer proliferation,lose the ability to regenerate after heart injury.Mi R-19a/19 b promoted the cardiomyocytes proliferation,but the proliferation was attenuated when the target gene pten was overexpressed,however the relationship between the tumor suppressor gene pten and the proliferation of cardiomyocytes was not clear.The tumor suppressor gene pten is a dual-specific phosphatase,which can dephosphorylate the second messenger PIP3 and affect the PI3K/AKT signaling pathway,thereby affecting cell survival.Studying the relationship between pten and cardiomyocyte proliferation is beneficial to the clinical treatment of MI.Objective To study the relationship between pten and mouse cardiomyocytes proliferation,cardiac regeneration after MI,and explore its mechanism.Materials and Methods Insert the lox P site at both end of exon 5 of pten gene,withα-MHC Mer Cre Mer to produce cardiomyocyte-specific pten knockout mice,using echocardiography to record the mice heart function after pten knockout.To investigate pten knockout mice heart function and cardiomyocyte proliferation after MI.Furthermore,test the mechanism of PTEN affecting cardiac function by transcriptome level RNA-sequencing.Results 1.The cardiomyocyte-specific pten knockout mouse were created successfully.2.Knock out pten in mouse cardiomyocytes can resist MI injury and improve heart function.3.Knock out pten in mice cardiomyocytes improved myocardial remodeling after MI and promote adult cardiomyocyte proliferation.4.Inhibition of PTEN activity can significantly increase the proliferation rate of cardiomyocytes in neonatal SD rats.5.Transcriptome sequencing showed that knock out pten in mouse cardiomyocytes reduced the expression of inflammation and fibrosis-related genes after MI.Conclusion Knock out pten in adult mice cardiomyocytes promote myocardial proliferation,reduce fibrotic damage,attenuate inflammatory response,and ultimately improve cardiac function.