| Arrhythmic right ventricular dysplasia/cardiomyopathy(ARVC/D)is an inherited disease caused mainly by a mutation in the desmosome gene.The phenotypic characteristic of ARVC is the replacement of cardiomyocytes by fibroadipocytes,which is a unique phenotype.However,due to the diversity of its pathogenesis and the complexity of its mechanism,there is no targeted treatment for ARVC in clinical practice.The treatment is generally based on the prevention and reference of other types of cardiomyopathy.Periostin(Postn)is an important component of the extracellular matrix,which is involved in cell adhesion and collagen organization.Periostin is expressed at baseline in healthy and mature hearts,but is significantly upregulated in damaged hearts.Several published studies have indicated that Periostin up-regulated plays an important role in the occurrence and development of various types of myocardial diseases,but the role of Periostin in ARVC is unknown.In this paper,we studied the role of Periostin in ARVC by using a mouse model that overexpressed a segment of truncated desmosome protein PG with abnormal function,and the results showed that Periostin was highly expressed in heart tissues of both ARVC patients and ARVC mouse models.We knocked out the Postn in ARVC mice,and the results showed that the knockout of Postn significantly improved the structural abnormalities of the hearts in ARVC mice,reduced myocardial hypertrophy and remodeling,and reduced the infiltration of fibroadipocytes.At the same time,the heart pumping ability of the ARVC mice was also significantly enhanced,and abnormalities in electrical conduction in the hearts were improved.By isolated cells in vitro and immunofluorescence labeling of heart tissues,we found that Periostin with high expression in ARVC may mainly come from cardiac fibroblasts.These findings may provide a new diagnostic marker and therapeutic target for the diagnosis and treatment of ARVC patients. |
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