Special Issue: Moving Heart Failure to Heart Success: Mechanisms, Regeneration & Therapy
Summary: This Editorial introduces DMM's new Special Issue on ‘Moving heart failure to heart success’. The Guest Editors reflect on how articles in the issue advance the cardiac research field.
A MODEL FOR LIFE
Summary: Xenotransplantation of porcine hearts is a potential option for patients with terminal heart failure who cannot receive human organs. Genetic modifications of source pigs were essential for successful heart replacement experiments in baboons, paving the way to clinical studies.
AT A GLANCE
Summary: We provide a systematic overview of currently available in vitro cardiac models, their method of generation, properties and examples for applications. Moreover, each model's advantages and limitations are discussed.
Summary: Despite remaining challenges, recent advances in genome editing, particularly with prime and base editors, offer exciting new possibilities for modeling and treating genetic cardiomyopathies.
Summary: This Review summarizes the development, function and dysfunction of the sinoatrial node, the primary pacemaker of the mammalian heart.
Summary: We conceptualize how phenotypes of syndromic congenital diseases affecting the cardiovascular system link to disrupted mechanisms in shared progenitor cells and developmental programs in the lateral plate mesoderm.
Summary: We provide evidence that transplantation of immature engineered heart tissue (EHT) patches without precultivation is feasible, with similar, or even slightly better, engraftment results than those obtained with matured EHT.
Deficiency in hereditary hemorrhagic telangiectasia-associated Endoglin elicits hypoxia-driven heart failure in zebrafish
Summary: CRISPR/Cas9-engineered Endoglin deficiency in zebrafish recapitulates critical aspects of hereditary hemorrhagic telangiectasia (HHT) and thus provides a valuable model for use in large-scale screens of HHT-active compounds.
A gut microbiome metabolite paradoxically depresses contractile function while activating mitochondrial respiration
Summary: Acute exposure of mouse hearts to trimethylamine-N-oxide levels reported in human disease differentially depresses cardiac contractile function while inappropriately activating mitochondrial respiration at Complexes I and II.
Piglet cardiopulmonary bypass induces intestinal dysbiosis and barrier dysfunction associated with systemic inflammation
Summary: Using a piglet model of cardiopulmonary bypass, we demonstrate significant changes in the microbiome, a key regulator of health and homeostasis, and evidence of intestinal barrier dysfunction following cardiopulmonary bypass associated with systemic inflammation.
A DUSP6 inhibitor suppresses inflammatory cardiac remodeling and improves heart function after myocardial infarction
Summary: Treatment with the small-molecule DUSP6 inhibitor BCI improves heart function and prevents abnormal cardiac remodeling by suppressing macrophage formation and inflammation after myocardial infarction in rats.
Maternal heterozygosity of Slc6a19 causes metabolic perturbation and congenital NAD deficiency disorder in mice
Summary: Slc6a19, encoding a neutral amino acid transporter, is the first non-enzymatic component of NAD metabolism shown to contribute to congenital NAD deficiency disorder, characterised by multiple malformations and embryo loss.
Summary: Administration of TH1834 mitigated the damaging effects of myocardial infarction in mice, supporting the possibility that Tip60 acetyltransferase inhibitors may be useful for the treatment of ischemic heart disease.
Drug-based mobilisation of mesenchymal stem/stromal cells improves cardiac function post myocardial infarction
Summary: Evaluation of a drug-based mobilisation approach as a potential alternative to transplantation-based cell therapy by using mesenchymal stem/stromal cells for cardiac repair.
Acute frataxin knockdown in induced pluripotent stem cell-derived cardiomyocytes activates a type I interferon response
Summary: In induced pluripotent stem cell-derived cardiomyocytes, acute frataxin knockdown, which compromises iron-sulfur cluster biogenesis, is associated with mitochondrial dysfunction and activation of a type I interferon response by cytosolic mitochondrial DNA.
Summary: The epicardium is required to promote cardiomyocyte growth during ventricular development at least in part via the FGF and VEGF signaling pathways.
Cardiac-specific Trim44 knockout in rat attenuates isoproterenol-induced cardiac remodeling via inhibition of AKT/mTOR pathway
Summary: This is the first study to demonstrate the function of Trim44 in the heart at baseline and under pathological stress. Trim44 could be a novel therapeutic target for prevention of cardiac hypertrophy.
Summary: Systematic investigation of Genomics England PanelApp genes associated with monogenic forms of cardiovascular disease reveals that the International Mouse Phenotyping Consortium is a valuable resource for understanding pleiotropic gene effects.
Application of an F0-based genetic assay in adult zebrafish to identify modifier genes of an inherited cardiomyopathy
Editors' choice: Owing to modifier genes, phenotypes of many human diseases that harbor identical causal mutations can vary substantially. Using a BAG3-associated cardiomyopathy zebrafish model, we demonstrated the feasibility of a F0-based genetic assay that enables rapid discovery of disease modifiers.