Arrhythmogenic cardiomyopathy(ACM)is one of the most common inherited cardiomyopathies,characterized by progressive fibrofatty replacement in the myocardium.However,the cellular origin of cardiac adipocytes in ACM rem...Arrhythmogenic cardiomyopathy(ACM)is one of the most common inherited cardiomyopathies,characterized by progressive fibrofatty replacement in the myocardium.However,the cellular origin of cardiac adipocytes in ACM remains largely unknown.Unraveling the cellular source of cardiac adipocytes in ACM would elucidate the underlying pathological process and provide a potential target for therapy.Herein,we generated an ACM mouse model by inactivating desmosomal gene desmoplakin in cardiomyocytes;and examined the adipogenic fates of several cell types in the disease model.The results showed that SOX9^(+),PDGFRa^(+),and PDGFRb^(+)mesenchymal cells,but not cardiomyocytes or smooth muscle cells,contribute to the intramyocardial adipocytes in the ACM model.Mechanistically,Bmp4 was highly expressed in the ACM mouse heart and functionally promoted cardiac mesenchymal-to-adipose transition in vitro.展开更多
基金supported by the National key R&D Program of China(2018YFA0108100,2018YFA0108700,2017YFA0105602)the National Natural Science Foundation of China(31871474,81720108004,81974019)+7 种基金the Chinese Postdoctoral Science Foundation(2022M710144)the“Shuguang Program”supported by Shanghai Education Development Foundation and Shanghai Municipal Commission(17SG54)Shanghai Rising-Star Program(20QA1406900,22QA1409300)the Research Team Project of Natural Science Foundation of Guangdong Province of China(2017A030312007)the Science and Technology Planning Project of Guangdong Province(2022B1212010010)the Key Program of Guangzhou Science Research Plan(201904020047)the Special Project of Dengfeng Program of Guangdong Provincial People’s Hospital(DFJH201812,KJ012019119,KJ012019423)the Shanghai Tech University Start-Up Fund。
文摘Arrhythmogenic cardiomyopathy(ACM)is one of the most common inherited cardiomyopathies,characterized by progressive fibrofatty replacement in the myocardium.However,the cellular origin of cardiac adipocytes in ACM remains largely unknown.Unraveling the cellular source of cardiac adipocytes in ACM would elucidate the underlying pathological process and provide a potential target for therapy.Herein,we generated an ACM mouse model by inactivating desmosomal gene desmoplakin in cardiomyocytes;and examined the adipogenic fates of several cell types in the disease model.The results showed that SOX9^(+),PDGFRa^(+),and PDGFRb^(+)mesenchymal cells,but not cardiomyocytes or smooth muscle cells,contribute to the intramyocardial adipocytes in the ACM model.Mechanistically,Bmp4 was highly expressed in the ACM mouse heart and functionally promoted cardiac mesenchymal-to-adipose transition in vitro.
