Genetic lineage tracing identifies cardiac mesenchymal-to-adipose transition in an arrhythmogenic cardiomyopathy model.

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

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.

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

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