Cardiomyocytes stimulate angiogenesis after ischemic injury in a ZEB2-dependent manner

The disruption in blood supply due to myocardial infarction is a critical determinant for infarct size and subsequent deterioration in function. The identification of factors that enhance cardiac repair by the restoration of the vascular network is, therefore, of great significance. Here, we show that the transcription factor Zinc finger E-box-binding homeobox 2 (ZEB2) is increased in stressed cardiomyocytes and induces a cardioprotective cross-talk between cardiomyocytes and endothelial cells to enhance angiogenesis after ischemia. Single-cell sequencing indicates ZEB2 to be enriched in injured cardiomyocytes. Cardiomyocyte-specific deletion of ZEB2 results in impaired cardiac contractility and infarct healing post-myocardial infarction (post-MI), while cardiomyocyte-specific ZEB2 overexpression improves cardiomyocyte survival and cardiac function. We identified Thymosin β4 (TMSB4) and Prothymosin α (PTMA) as main paracrine factors released from cardiomyocytes to stimulate angiogenesis by enhancing endothelial cell migration, and whose regulation is validated in our in vivo models. Therapeutic delivery of ZEB2 to cardiomyocytes in the infarcted heart induces the expression of TMSB4 and PTMA, which enhances angiogenesis and prevents cardiac dysfunction. These findings reveal ZEB2 as a beneficial factor during ischemic injury, which may hold promise for the identification of new therapies

Single-Cell RNA Sequencing of the Adult Mammalian Heart—State-of-the-Art and Future Perspectives

Purpose of the Review: Cardiovascular disease remains the leading cause of death worldwide, resulting in cardiac dysfunction and, subsequently, heart failure (HF). Single-cell RNA sequencing (scRNA-seq) is a rapidly developing tool for studying the transcriptional heterogeneity in both healthy and diseased hearts. Wide applications of techniques like scRNA-seq could significantly contribute to uncovering the molecular mechanisms involved in the onset and progression to HF and contribute to the development of new, improved therapies. This review discusses several studies that successfully applied scRNA-seq to the mouse and human heart using various methods of tissue processing and downstream analysis. Recent Findings: The application of scRNA-seq in the cardiovascular field is continuously expanding, providing new detailed insights into cardiac pathophysiology. Summary: Increased understanding of cardiac pathophysiology on the single-cell level will contribute to the development of novel, more effective therapeutic strategies. Here, we summarise the possible application of scRNA-seq to the adult mammalian heart