Grune et al. show that hypokalemic mice develop spontaneous ventricular tachycardia after myocardial infarction, and they use this model to dissect the role of immune cells in arrhythmia: neutrophils increase ventricular tachycardia, partly by promoting reactive oxygen species production, whereas efferocytic macrophages play a protective role.

Zhao et al. show that, in patients with coronary artery disease, CD4⁺ T cells present a blunted response to SARS-CoV-2 and Epstein–Barr viral antigens, due to the overexpression of the immune checkpoint CD155 in macrophages, primed by the exposure to low-density lipoprotein and its oxidized form. The experiments show that CD155 overexpression is due to stabilizing post-translational modifications mediated by the mRNA methylase MTTL3.

Ngwenyama et al. show that cardiac fibroblasts express MHCII during cardiac inflammation, and are able to process extracellular proteins into small peptides that induce CD4⁺ T cell immune responses. Conditional deletion of MHCII in cardiac fibroblasts ameliorates cardiac remodeling and dysfunction induced by cardiac pressure overload, supporting a central role for cardiac fibroblast MHCII in antigen presentation and in cardiac fibrosis and dysfunction in experimental HF.

In this Review, the authors provide an overview of the critical studies reporting Cre and CreER toxicity in the cardiovascular system, discuss the mechanisms proposed to underlie Cre toxicity and highlight the need to understand, eliminate and control for Cre/CreER toxicity in each experimental model.

Depuydt and Schaftenaar et al. profile the T cell clonality in patients with atherosclerosis by performing single-cell T cell receptor sequencing on carotid artery plaques and matched peripheral blood mononuclear cell samples. The analyses showed plaque-specific clonal expansion in effector CD4⁺ T cells, expressing genes indicative of exposure to activating antigens, thus suggesting that atherosclerosis has an autoimmune component driven by autoreactive CD4⁺ T cells.

Zekavat, Matesanz, Viana-Huete et al. show an increased risk of peripheral artery disease and atherosclerosis in different vascular beds in patients with clonal hematopoiesis of indeterminate potential (CHIP) caused by mutations in DNA damage repair genes, such as TP53. Validations in a mouse model support the causal contribution of TP53-mutant CHIP to atherosclerosis.

Berg Luecke et al. developed an analytical platform, CellSurfer, that enables the quantitative profiling of cell surface proteome (surfaceome) from small samples, and they apply it to primary human heart cells. The analyses revealed LSMEM2 as a surface protein specific for healthy cardiomyocytes; important surfaceome differences between primary human cardiac cells and the pluripotent stem cell derivatives; and differences in the abundance of surface proteins between human failing and non-failing cardiomyocytes.

Deviatiiarov, Gams et al. provide an atlas of the actively transcribed regulatory elements (promoters and enhancers) in the human heart by performing cap analysis of gene expression (CAGE) on 21 healthy donor hearts and ten failing hearts from ischemic and non-ischemic cardiomyopathy. The data show how the alternative use of regulatory elements modulates the differential gene expression across different heart chambers, disease states and disease types.

In a phase II, randomized, placebo-controlled, double-blind cross-over trial, Jama et al. show that delivery of short-chain fatty acids via acetylated and butyrylated high-amylose maize starch (HAMSAB) supplementation result in a clinically relevant reduction in 24-hour systolic blood pressure in patients with essential hypertension.

By conducting a large multi-ancestry GWAS of varicose veins followed by bioinformatics analyses, Levin et al. identified new and recurrent causal variants, traits with shared genetic mechanisms, and putative causal risk factors of the disease, revealing its polygenic architecture and genetic overlap with arterial and venous disease and identifying potential therapeutic targets.

The rapid development of single-cell transcriptomics, epigenomics, proteomics and metabolomics has resulted in a wave of new biological discoveries. Here we explore what this has meant for the cardiovascular field and what the future might hold for developing treatments for patients.

Nature Cardiovascular Research is one year old. We look back at our first year and look forward to the years to come, grateful to our authors and audience for their contribution and support.

Pregnancy is associated with a substantial risk of short-term and long-term cardiovascular diseases. Here we discuss physiological and social factors that affect the risk of pregnancy-related cardiovascular diseases and opportunities to improve outcomes.

Iron is essential to the production of myocardial energy and proteins critical for cardiovascular function. Nearly 50% of patients with heart failure with reduced ejection fraction (HFrEF) meet current criteria for iron deficiency, and there has been considerable interest in intravenous repletion of iron stores as a therapeutic strategy to improve HFrEF outcomes. However, the data on intravenous iron therapy in HFrEF have been mixed.