Effects Of Periostin Knockout On Arrhythmogenic Right Ventricular Cardiomyopathy Induced By Desmosome DSP Mutation In Mice

ARVC is a kind of heart disease caused by injury and death of cardiac myocyte and then cardiac remodeling through cardiac fibrosis,which can eventually lead to cardiac dysfunction or even sudden death.The occurrence of ARVC is mainly caused by the mutation of desmosome gene.The destruction of desmosome structure affects the stable connection and signal transmission between myocardial cells,resulting in the injury of myocardial cells.The occurrence of ARVC is not limited to the right ventricle,and many patients have bilateral ventricular involvement or more severe left ventricle disease.However,the clinical diagnosis of ARVC is difficult at present,and there are no specific drugs for treatment.We hope to open up new research area from the perspective of extracellular matrix proteins.Extracellular matrix is an essential component during cardiac remodeling.As one of extracellular matrix proteins,periostin is expressed very low in normal heart,high expression of periostin can be detected only during the development of the heart or the process of cardiac remodeling.Current studies have shown that periostin plays an important role in fibrosis,and is closely related to heart failure and myocardial infarction caused by fibrosis,but the function of periostin in ARVC is not clear.In our study,we used the ARVC mouse model with DSP knockout to study the function of periostin in ARVC.The results show that the expression of periostin is upregulated in heart tissues of ARVC patients and ARVC mice with DSP knockout.Periostin is mainly expressed by fibroblast,distributed in and around the fibrosis area,and periostin can be detected in the process of ARVC disease,so periostin may play an importarn role in the fibrosis of ARVC.Our further study found that periostin knockout in ARVC mice significantly restores the degree of cardiac fibrosis.The ejection fraction,ventricular cavity size and other cardiac functions of ARVC mice are also alleviated to some extent.Furthermore,periostin knockout reduces the apoptosis of cardiac myocytes during the early growth of ARVC mice.In summary,periostin is highly expressed in the hearts of ARVC mice and ARVC patients.Periostin knockout significantly alleviates the occurrence of cardiac fibrosis and improves cardiac function in ARVC mice.