Bernier-Latmani et al. report a mechanism for maintaining colon cancer-associated vasculature, in which colon endothelial apelin signaling promotes migration of distant venous endothelial cells toward the tumor progenitor cell niche to sustain VEGFA-independent vascular expansion and a normoxic microenvironment.

Popescu et al. developed a deep learning approach that blends neural networks and survival analysis to predict patient-specific survival curves from raw contrast-enhanced cardiac magnetic resonance images and clinical covariates for patients with ischemic heart disease to offer accurate arrhythmic sudden death predictions.

In a multicenter research program coordinated by the International Mouse Phenotyping Consortium, Spielmann et al. analyze the cardiac function and structure in ~4,000 monogenic mutant mice and identify 705 mouse genes involved in cardiac function, 75% of which have not been previously linked to cardiac heritable disease in humans. Using the UK Biobank human data, the authors validate the link between cardiovascular disease and some of the newly identified genes to illustrate the resource value and potential of their mutant mouse collection.

Using high-resolution confocal images and computational surface mapping, Esteban et al. provide a detailed pseudodynamic atlas of early heart tube development (E7.5–E8.5), develop a morphometric staging system based on landmark curves and distances in the surface of the tissues and identify parameters that can be used for precise embryo staging across different labs. This morphometric analysis reveals early signs of left–right asymmetry, before the cardiac looping stage, which is regulated by the Nodal signaling pathway.

Pianca and Sacchi et al. unveil an important role for glucocorticoids and their receptor (GR) in cardiomyocyte cytoarchitectural/metabolic maturation, cell cycle exit and loss of regenerative ability, and they propose GR antagonization as a strategy for heart regeneration.

Yu et al. show that Piezo1 is the stretch-activated mechanosensor that provides the calcium source to activate TRPM4 and the downstream CaMKII-HDAC4-MEF2 pathway, a key mediator in the cardiomyocytes’ hypertrophic response in pressure overload models.

Boon et al. show that thalidomide appears to be efficacious in the management of chronic pain, bleeding and ulceration in 18 patients with severely symptomatic arteriovenous malformations refractory to conventional therapies.

Hansmann et al. show that serial intravascular infusions of conditioned media produced by allogenic umbilical cord mesenchymal stem cells markedly improved the clinical features of a young child with severe pulmonary arterial hypertension. The multi-omic approach analyzing the transcriptome and the proteome of these stem cells isolated from four donors provides initial insight into their beneficial paracrine function.

Using high-resolution confocal images and computational surface mapping, Esteban et al. provide a detailed pseudodynamic atlas of early heart tube development (E7.5–E8.5), develop a morphometric staging system based on landmark curves and distances in the surface of the tissues and identify parameters that can be used for precise embryo staging across different labs. This morphometric analysis reveals early signs of left–right asymmetry, before the cardiac looping stage, which is regulated by the Nodal signaling pathway.

Increased late sodium current due to the disruption of voltage-gated sodium channel inactivation is a common pathogenic mechanism in different arrhythmogenic syndromes. Chakouri et al. show that fibroblast growth factor homologous factors (FHFs) modulate pathogenic late sodium current in an isoform-specific way, and leverage this observation to design and test a prototype of inhibitor peptide based on a protein domain from an inhibitory FHF isoform.

Recognition of mechanistic similarities and the interconnection between cardiovascular disease and cancer in recent years offers an opportunity to think more creatively about therapeutic development. Targeting shared pathways, either through drug repurposing or novel compounds, holds the promise of addressing both afflictions at the same time.

Fibrosis is a common sequela of cardiovascular disease that results in structural and functional changes. Targeting the subsets of pathogenic cardiac fibroblasts may be an attractive option for reducing morbidity that is associated with heart disease, but the timing, specificity and extent to which fibroblast-targeting therapies might be used is still debated.