Reviews & Analysis

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.

In coronary artery disease, the transition from an apparently stable state to a life-threatening acute cardiac event is difficult to predict. As such, a recent study applied proteomic and metabolomic approaches to discover new biomarkers that signal imminent myocardial infarction.

Defects in platelet adhesion at sites of injury can lead to excessive bleeding. A study by Gandhi et al. investigates a new bispecific antibody as a possible therapy to prevent bleeding in patients with inherited defects in platelet adhesion.

Myocardial infarction causes endoplasmic reticulum (ER) stress, thereby triggering the release of a set of poorly defined growth factors. A study shows that the growth factor CRELD2 is secreted in response to ER stress and is required for preserving heart function after myocardial infarction in mice.

Cerebrospinal fluid is now thought to drain through lymphatics instead of veins, but the routes the fluid takes from the subarachnoid space to cervical lymph nodes are unclear. Using advanced imaging, a recent study provides unprecedented anatomical details of lymphatic vessels draining cerebrospinal fluid along the nasopharynx.

Regulatory T cells are cardinal players in cardiovascular disease. Research now identifies a noncanonical chemokine signaling pathway that governs the responsiveness and effector functions of these cells in atherosclerosis.

Goerlich et al. review the current knowledge of the cardiovascular complications of the post-COVID condition, including postural orthostatic tachycardia syndrome, myocardial injury, heart failure, myocarditis and arrhythmias, highlighting currently available and potential treatments.

In acute myocardial infarction treated with reperfusion, functional preservation of myocardium requires an angiogenic response. A new study shows that CRELD2, an endoplasmic reticulum (ER)-resident protein induced in response to ER stress, acts as an angiocrine factor to limit cardiac dysfunction after ischemia/reperfusion injury in mice.

Clonal hematopoiesis of indeterminate potential (CHIP) is a risk factor for cardiovascular disease. Neutralization of the cytokine IL-1β (as in the CANTOS clinical trial) resulted in a greater reduction in adverse cardiovascular events in patients with CHIP than the reduction in molecularly unstratified patients. New research reveals that some of the cardiovascular benefits of anti-IL-1β therapy in patients with CHIP might be delivered by an improvement in plaque stability via increased fibroblast-like cells.

Pro-reparative cardiac-resident macrophages have emerged as major players in salvaging the ischemic myocardium of a diseased heart. New research now highlights ATF3 as a key transcription factor that governs macrophage survival and proliferation and myocardial repair.

GPR15 is a chemoattractant-G protein-coupled receptor that mediates homing of T cells. Stoffers et al. present insights into how GPR15 mediates the recruitment of cytotoxic T cells to contain and clear coxsackievirus B3 from the heart and regulatory T cells to limit immune pathology.

Physical simulators of organs can have great impact on diagnostic and surgical training. A novel biohybrid platform to simulate the right ventricle of the heart with high fidelity has been developed and tested, demonstrating that this is a valid alternative to in vivo experimentation.

Timothy syndrome is a severe variant of long QT syndrome, but an accurate in vivo model to study the disease and identify treatments has been lacking. A knock-in swine model of Timothy syndrome now shows that CaMKII-mediated reduction in peak I_Na slows the cardiac impulse propagation and contributes to the severe arrhythmia in the disorder.

Xie et al. discuss the strengths and limitations of induced cardiomyocyte-like cell reprogramming, the progress made in the past decade, with a focus on single-cell '-omics' research, and the obstacles that remain to be overcome for clinical application.

Raposo-Gutiérrez et al. review the recent knowledge on adaptive immunity in atherosclerosis, the identity of antigens driving the immune response and how to exploit antigen specificity in possible immunomodulatory strategies, including vaccination.

A key consequence of increased and sustained vascular permeability in several inflammatory and cardiovascular disorders is the development of interstitial protein-rich proinflammatory edema. This response remains poorly understood mechanistically and its potential adverse effect on local and systemic diseases is often underestimated. To discuss current findings and identify crucial unresolved questions, a workshop was held in Berlin from 12–15 April 2023. Key topics that were discussed included regulation of endothelial cell junctions, neutrophil-dependent vascular leakage, resolution of edema, exemplar diseases, and anti-edema therapies. This report is a summary of the meeting.

Arrhythmogenic cardiomyopathy is a major cause of sudden death among young people. Three studies show that gene therapy to restore the desmosomal protein PKP2 holds promise in improving the prognosis of affected individuals.

Environmental factors can contribute to congenital disorders, including heart defects and craniofacial malformations. Single-cell multi-omic analyses in mouse embryos from diabetic mothers (with high intrauterine glucose levels) revealed epigenetic changes in specific sub-populations of cardiac and craniofacial progenitors. These changes affected retinoic acid signaling and axial patterning, contributing to the observed developmental anomalies.

The molecular mechanisms that link propionyl-CoA metabolism and epigenetic regulation of gene expression are unclear, as are the implications for heart function. Now, new insights into the modulation of chromatin acylation and transcription by aberrant oxidation of propionyl-CoA are revealed in the dysfunctional hearts of mice with propionic acidemia.

Coronary artery calcification (CAC) is a strong predictor of coronary artery disease. A genome-wide association study of CAC in diverse populations, including 22,400 participants, identifies two previously unrecognized loci associated with CAC and provides insights into the underlying molecular mechanism of CAC.