Articles in 2026

Pathogenic variants in RBM20, which encodes a cardiac splicing factor, lead to an aggressive form of dilated cardiomyopathy with a high risk of ventricular arrhythmias. This study shows that genetic or pharmacological inhibition of CAMK2D, one of the RBM20 splicing targets, rescues cardiac dysfunction in mouse models of RBM20.

Cardiac allograft vasculopathy, a major cause of retransplantation and death, has been largely linked to T cells and donor-specific antibodies causing endothelial injury and chronic vascular proliferation. A study now highlights a key complementary role for innate immune cell crosstalk, especially by macrophages, in driving disease progression.

Owen et al. used single-cell RNA sequencing and spatial transcriptomics to analyze graft cells in heart transplants with cardiac allograft vasculopathy, showing that vascular smooth muscle cells and macrophages drive interferon-mediated inflammation and that JAK signaling blockade prolongs allograft survival.

Khurana et al. share their perspective on healthcare system preparedness in sub-Saharan Africa in light of the recent increase in ischemic heart disease burden, highlighting areas that require intervention to improve the management of this noncommunicable condition in the region.

Hu et al. show that the transmembrane glycoprotein CD98hc in cerebral endothelial cells regulates the integrin–FAK signaling pathway, thereby promoting angiogenesis and maintaining blood–brain barrier integrity.

To understand and prevent life-threatening heart arrhythmias, integrating tissue structure and function is essential. Merging panoramic optical mapping with AI-assisted microCT reconstruction permits simultaneous assessment of electrical and structural properties to study arrhythmia mechanisms at high electrical and structural resolution.

Pathogenic variants in RBM20 cause an aggressive form of heart disease. van den Hoogenhof et al. show that overactivated CAMK2D drives this disease, and that pharmacological CAMK2D inhibition is a promising therapeutic approach in patients with RBM20 cardiomyopathy.

Atrial fibrillation is linked to fibrosis and inflammatory macrophage recruitment in atria, with osteopontin (encoded by Spp1) increasing susceptibility by promoting atrial fibrosis and uneven conduction. Research shows that antibody-based silencing of Spp1 in some TREM2⁺ macrophages reduces fibrotic remodeling and atrial fibrillation risk.

In this Review, Xia et al. discuss the potential of colchicine as a therapy for atherosclerotic cardiovascular disease, highlighting evidence from clinical trials and mechanistic studies showing its effects on vascular inflammation, plaque stability, and immune and vascular cell function. They also emphasize that mixed results in recent cardiovascular and cerebrovascular trials highlight the need to integrate mechanistic insights with clinical evidence to refine colchicine use and guide precision anti-inflammatory strategies.

Momin et al. develop an antibody–siRNA conjugate to inhibit the secretion of osteopontin by the TREM2⁺ macrophages that expand during human atrial fibrillation. In mice, this approach reduced fibrosis and atrial fibrillation vulnerability.

Splice-altering genetic variants are found in individuals with infantile cardiomyopathy, but the consequences are unclear. A study now shows that aberrant splicing of only one exon in the AARS2 gene can cause devastating heart development defects, phenocopying patient congenital cardiomyopathy.

Lu et al. report that PCBP1 safeguards AARS2 alternative splicing in the heart, and that loss of PCBP1 disrupts AARS2 splicing, leading to infantile mitochondrial cardiomyopathy. Loss of cardiac PCBP1 or AARS2 impairs oxidative phosphorylation and activates mitonuclear signaling and the unfolded protein response pathway.

Melki, Avula and colleagues combine three-dimensional panoramic optical mapping with micro-computed tomography and deep learning to generate structural and electrical activation data of the heart and elucidate mechanisms of conduction abnormalities.

Apheresis, introduced 50 years ago, remains a crucial therapy for homozygous familial hypercholesterolemia, a rare gene disorder that causes extreme LDL-cholesterol levels and early cardiovascular death. This Comment also honors the late professor Thompson, a pioneer of apheresis, whose work helped to shape the field.

Zhou et al. review recent technological advances in mRNA-based biotechnologies for cardiovascular disease, examining preclinical applications, clinical trial outcomes, and the key challenges and future directions of these approaches.

How fetal and adult hematopoietic programs are organized in the embryo has remained a long-standing question. Using lineage tracing in mice, we identified a subset of specialized fetal blood progenitors that originate from the hemogenic endothelium of the embryonic vitelline and umbilical arteries. These fetal hematopoietic cells underlie a previously unrecognized developmental wave of hematopoiesis.