The Function Of Heat Shock Protein 60 (HSP60) In The Cardiac Development

Congenital heart disease is the most common of all birth defects.Although significant advances have been made in surgery and medical treatment for congenital heart disease,many interventional treatments are conservative rather than curative.Some survivors still have significant hemodynamic and electrical conduction abnormalities,and experience long-term cardiovascular complications.Considering the high incidence and mortality rate of congenital heart disease,and the inducibility of cardiovascular disease after birth,it is particularly important to directly study the pathological causes of the occurrence and development of congenital heart disease.More and more studies have shown that mitochondrial dysfunction is an important marker of cardiomyocyte dysfunction and death,and a large number of studies have also found that changes in mitochondrial structure,function and other homeostasis are important for heart development,embryonic survival and normal heart function.As an important part of the mitochondrial protein quality control system,mitochondrial chaperones lay the foundation for maintaining mitochondrial structure and function homeostasis.Heat shock protein 60(HSP60)is a chaperone protein mainly existing in mitochondria.It has been found that the mutation of HSP60 gene is associated with human genetic diseases.Studies of these genetic disorders suggest that HSP60 may play an important role in the normal development and function of the nervous system and tissues throughout the body.Moreover,studies have shown that HSP60 is a key regulatory molecule for the maintenance and survival of cardiac structure and function in adult mice.However,the specific role and function of HSP60 in cardiac development remain unclear.To explore the role of HSP60 in embryonic heart development.In this study,Hsp60 conditional knockout mice(Hsp60f/f)were introduced and hybridized with α-MHC-Cre transgenic mice specifically expressing Cre recombinase to achieve HSP60 specific knockout in mouse cardiomyocytes.In this study,α-MHC-Cre recombinant enzyme was used to specifically knock out HSP60(α-MHC-Cre+,Hsp60f/f)in mouse cardiomyocytes,which resulted in abnormal cardiac development,mainly manifested as thinning of cardiac ventricular wall and decreased proliferation rate of cardiomyocytes.In the end,a large number of mice died at the embryonic stage of 14.5 days(E14.5)to E16.5 days.In addition,in order to explore the molecular mechanism of HSP60’s regulation of cardiac development,this study analyzed the changes in transcriptome level after HSP60 knockout by RNA-Seq technology.The results showed that HSP60 knockout affected the expression of p21 gene and PI3K-AKT signaling pathway,and then participated in the regulation of cardiomyocyte proliferation.In conclusion,this study demonstrated that HSP60 plays a crucial role in the development of mouse embryos heart by constructing cardiomyocytes specific knockout of HSP60 mice,and knockout of HSP60 in mouse cardiomyocytes can lead to abnormal development and mouse embryonic heart and embryonic death.At the same time,we also found that HSP60 knockout can regulate the PI3K-AKT signaling pathway and the expression of p21,which in turn affects the proliferation of cardiomyocytes.This study provides new experimental evidence for the development mechanism of congenital heart disease.