Single-Cell Transcriptomic Analysis Reveals Myocardial Fibrosis Mechanism of Doxorubicin-Induced Cardiotoxicity.

Myocardial fibrosis is a pathological feature of doxorubicin-induced chronic cardiotoxicity that severely affects the prognosis of oncology patients. However, the specific cellular and molecular mediators driving doxorubicin-induced cardiac fibrosis, and the relative impact of different cell populations on cardiac fibrosis, remain unclear.This study aimed to explore the mechanism of doxorubicin-induced cardiotoxicity and myocardial fibrosis and to find potential therapeutic targets. Single-cell RNA sequencing was used to analyze the transcriptome of non-cardiomyocytes from normal and doxorubicin-induced chronic cardiotoxicity in mouse model heart tissue.We established a mouse model of doxorubicin-induced cardiotoxicity with a well-defined fibrotic phenotype. Analysis of single-cell sequencing results showed that fibroblasts were the major origin of extracellular matrix in doxorubicin-induced myocardial fibrosis. Further resolution of fibroblast subclusters showed that resting fibroblasts were converted to matrifibrocytes and then to myofibroblasts to participate in the myocardial remodeling process in response to doxorubicin treatment. Ctsb expression was significantly upregulated in fibroblasts after doxorubicin-induced.This study provides a comprehensive map of the non-cardiomyocyte landscape at high resolution, reveals multiple cell populations contributing to pathological remodeling of the cardiac extracellular matrix, and identifies major cellular sources of myofibroblasts and dynamic gene-expression changes in fibroblast activation. Finally, we used this strategy to detect potential therapeutic targets and identified Ctsb as a specific target for fibroblasts in doxorubicin-induced myocardial fibrosis.

Application of Homograft Valved Conduit in Cardiac Surgery.

Valved conduits often correct the blood flow of congenital heart disease by connecting the right ventricle to the pulmonary artery (RV-PA). The homograft valved conduit was invented in the 1960s, but its wide application is limited due to the lack of effective sterilization and preservation methods. Modern cryopreservation prolongs the preservation time of homograft valved conduit, which makes it become the most important treatment at present, and is widely used in Ross and other operations. However, homograft valved conduit has limited biocompatibility and durability and lacks any additional growth capacity. Therefore, decellularized valved conduit has been proposed as an effective improved method, which can reduce immune response and calcification, and has potential growth ability. In addition, as a possible substitute, commercial xenograft valved conduit has certain advantages in clinical application, and tissue engineering artificial valved conduit needs to be further studied.