10× single-cell sequencing revealed cellular composition heterogeneity in cardiac myxoma with malignant glandular properties.

Cardiac myxoma is the most common primary cardiac tumor in adults. The histogenesis and cellular composition of myxoma are still unclear. This study aims to reveal the role of myxoma cell components and their gene expression in tumor development. We obtained single living cells by enzymatic digestion of tissues from 4 cases of surgically resected cardiac myxoma. Of course, there was 1 case of glandular myxoma and 3 cases of nonglandular myxoma. Then, 10× single-cell sequencing was performed. We identified 12 types and 11 types of cell populations in glandular myxoma and nonglandular myxoma, respectively. Heterogeneous epithelial cells are the main components of glandular myxoma. The similarities and differences in T cells in both glandular and nonglandular myxoma were analyzed by KEGG and GO. The most important finding was that there was active communication between T cells and epithelial cells. These results clarify the possible tissue occurrence and heterogeneity of cardiac myxoma and provide a theoretical basis and guidance for clinical diagnosis and treatment.

Cysteine and glycine rich protein 2 exacerbates vascular fibrosis in pulmonary hypertension through the nuclear translocation of yes-associated protein and transcriptional coactivator with PDZ-binding motif.

Pulmonary hypertension (PH) is a serious cardiovascular disease with a poor prognosis and high mortality. The pathogenesis of PH is complex, and the main pathological changes in PH are abnormal hypertrophy and vessel stiffness. Cysteine and glycine rich protein 2 (Csrp2), a member of the LIM-only family plays a key role in the response to vascular injury. However, its roles in vascular fibrosis and PH have not been clarified. Therefore, this study aimed to investigate whether Csrp2 can promote vascular fibrosis and to further explore the possible mechanisms. Csrp2 expression was increased in both the pulmonary vasculature of rats with PH and hypoxic pulmonary vascular smooth muscle cells (PASMCs). Hypoxia activated TGF-ß1 and its downstream effector, SP1. Additionally, hypoxia activated the ROCK pathway and inhibited KLF4 expression. Silencing SP1 and overexpressing KLF4 reversed the hypoxia-induced increase in Csrp2 expression. Csrp2 knockdown decreased the expression of extracellular matrix (ECM) proteins and inhibited the nuclear translocation and expression of YAP/TAZ in hypoxic PASMCs. These results indicate that hypoxia induces Csrp2 expression through the TGF-ß1/SP1 and ROCK/KLF4 pathways. Elevated Csrp2 promoted the nuclear translocation and expression of YAP/TAZ, leading to vascular fibrosis and the development of PH.

Supplementation with Tex261 provides a possible preventive treatment for hypoxic pulmonary artery hypertension.

Objectives: Pulmonary artery hypertension (PAH) is a serious disease for which there is no effective treatment. Its pathogenesis is complex and has not yet been clarified. Tex261 is a protein-coding gene whose functional enrichment nodes include the transporter activity of COP II. However, the role of Tex261 in PAH remains unknown. Methods: Sugen5416/Hypoxic PAH models were established, and pulmonary arteries (PAs) were isolated for proteomic sequencing. The binding sites between Hif-1α and Tex261 were verified by dual-luciferase reporter gene assay. Cell proliferation was detected by MTS and EdU assays. For determination of the preventive and therapeutic effects of Tex261, intratracheal instillation of adeno-associated virus (AVV6) with Tex261 vectors was performed. Results: Tex261 was screened according to the proteomic sequencing data. Hif-1α inhibited Tex261 promoter activity under hypoxia. Decreased Tex261 expression promoted PASMC proliferation. Tex261 regulated Sec23 via the Ndrg1-mediated Akt pathway. Tex261 overexpression improved the pressure and vessel remodeling of PAs induced by Sugen5416/hypoxia. Conclusion: Hypoxia suppressed Tex261 expression through Hif-1α activation. The decreased Tex261 could promote Ndrg1 and depress Akt activity and then inhibit Sec23 activity, which leads to cell proliferation and vessel remodeling. Elevated Tex261 has some preventive and therapeutic effects on rats with PAH.