Cardiac regeneration articles from across Nature Portfolio

Adult hearts have inherently limited regenerative capabilities, such that injury results in lasting damage. The situation is different in neonatal mouse hearts, however, where a new study reveals a role for the immunomodulatory PD-1–PD-L1 pathway in regulating regeneration after injury.

Non-coding RNAs are implicated in the pathophysiology of ischaemic heart disease and heart failure. In this Review, Caporali and colleagues examine the biology of these molecules and discuss the potential of non-coding RNAs for translation to the clinic as biomarkers and therapeutics in adverse cardiac remodelling leading to ischaemic heart failure.

Here, Ma et al. investigate the translational profile of cardiac regeneration, pointing to Nat10 as a key regulator of cardiomyocyte proliferative potential, and describing how it regulates cardiac gene expression.

Vargas Aguilar et al. report that the PD-1–PD-L1 checkpoint-inhibitor pathway is highly active in heart-resident and circulating immune cells of newborn mice and disruption of this pathway led to increased inflammation and pathogenic T cell activity, impairing regeneration.

Using single-cell RNA sequencing, spatial transcriptomics and genetic experiments, Li et al. report that the close interaction of a specific cardiomyocyte subtype (aCM2), fibroblasts expressing the complement C3 and macrophages expressing C3ar1 was observed in pro-renewal conditions, such as regenerative neonatal hearts and hearts of adult mice overexpressing an active form of YAP in cardiomyocytes.

Selvakumar, Clayton et al. use a porcine model of myocardial infarction and PSC-CM transplantation and identify atrial and pacemaker-like cardiomyocytes as the cause of engraftment arrhythmias and surface marker signatures to distinguish between arrhythmogenic and non-arrhythmogenic cardiomyocytes.

Enhancing vascularization to improve cardiac disease outcomes is a therapeutic approach with limited success. Here, the authors show that cardiac repair is governed by spatiotemporally regulated programs and underline the signaling mechanisms driving vascular deterioration.

Adult hearts have inherently limited regenerative capabilities, such that injury results in lasting damage. The situation is different in neonatal mouse hearts, however, where a new study reveals a role for the immunomodulatory PD-1–PD-L1 pathway in regulating regeneration after injury.

Inhibition of MEIS1–HOXB13 activity by the aminoglycosides neomycin and paromomycin facilitates cardiomyocyte proliferation and heart regeneration.

An article in Nature reports a leadless photoelectrochemical device that exploits a new type of diode junction to regulate heartbeats by light.

The cellular microenvironment and interplay between cell types are essential for cardiac renewal. Combined single-cell and single-nucleus sequencing, spatial transcriptomics and loss-of-function experiments in constitutively YAP-expressing infarcted hearts reveal a cellular triad and complement signaling that evoke renewal of heart muscle.

The metabolic maturation of mammalian cardiomyocytes that occurs during the early postnatal period shapes the epigenetic landscape of cardiomyocytes and creates a barrier for cell division, but reversing this remodelling process can restore the reparative capacity of the heart in mice, according to a study published in Nature.

An intravascularly infused extracellular matrix preparation binds to leaky microvasculature, thereby localizing to inflamed tissues and promoting repair and regeneration, and potentially healing damaged tissues ‘from the inside out’.