Reviews & Analysis

Macrophage–fibroblast interactions have a central role in cardiac fibrosis. In response to left ventricular pressure overload, CCR2⁺ cardiac macrophages acquire a fibrogenic phenotype, secreting IL-1β and promoting the activation of a FAP⁺ POSTN⁺ fibroblast subpopulation through the transcription factor MEOX1. Macrophage-derived fibroblast-activating cytokines (such as IL-1β), growth factors and matricellular proteins contribute to the pathogenesis of heart failure.

Cholesterol crystals (CCs) have a pathogenic role in various cardiovascular diseases, particularly atherosclerosis. In this Review, Boisvert and colleagues describe the mechanisms underlying CC formation and the role of CCs in cardiovascular disease, as well as therapeutic approaches aimed at reducing CC-mediated atherosclerotic burden.

Cell therapy has emerged in the past 20 years as a promising avenue for cardiac repair and regeneration. In this Review, Zhang and colleagues provide an overview of the evolution of cell-based and cell product-based therapies for the treatment of heart failure, including challenges and lessons learned, and summarize ongoing clinical trials on the feasibility of novel or underexplored treatment protocols.

In this Review on cardiodermatology, Gelfand and colleagues discuss specific skin findings associated with cardiovascular diseases, important cutaneous adverse effects of common cardiovascular therapies, and the effects of dermatological diseases and dermatological treatment on cardiovascular risk.

In this Review, Tao and colleagues discuss the design and applications of nanoparticles and nanofabricated biomaterials, such as hydrogels, external graft support devices and cell-based therapies, for the treatment of vein graft disease and highlight the potential of using these nanofabricated biomaterials alongside bypass surgery to improve local delivery efficiency and therapeutic efficacy.

In this Review, Rajagopalan and colleagues summarize the sources of greenhouse gas emissions related to the provision of cardiovascular health care and suggest strategies to reduce carbon emissions and costs, including the use of renewable energy, waste reduction and disease prevention.

In this Review, Schotten and colleagues summarize the latest knowledge on the molecular and cellular mechanisms of atrial fibrosis, describe the electrophysiological manifestations of atrial fibrosis, critically appraise the diagnostic tools to quantify atrial fibrosis, discuss emerging therapeutic interventions, and highlight knowledge gaps and future research directions.

Consumption of a high-fat diet leads to the progressive growth of atherosclerotic lesions. Two new studies document that, despite similar overall exposure to high-fat diet over a lifetime, an intermittent consumption of high-fat diet early in life accelerates atherosclerosis compared with continuous consumption of a high-fat diet. The mechanisms for accelerated atherosclerosis include reprogramming of macrophages and neutrophils.

In this Review, Mestroni and colleagues provide an overview of the pathophysiological mechanisms underlying dilated cardiomyopathy, including both genetic and non-genetic causes, and discuss the development of novel therapies, such as small molecules and gene therapy.

Invasive cardiovascular procedures are inherently associated with a risk of acute brain injury, both during and after the intervention. In this international Consensus Statement, the authors provide consensus recommendations on the prevention, diagnosis and treatment of acute brain injury caused by cardiovascular interventions.

In contrast to the ABYSS investigators’ interpretation of the primary results of their trial, we believe that β-blockers can be safely discontinued in the majority of patients after an uncomplicated myocardial infarction. However, in individuals developing symptoms of angina or heart failure, β-blocker treatment remains one of several guideline-recommended therapies.

In this Review, Münzel and colleagues describe the adverse effects of soil and water pollution, including heavy metal, pesticide, and microplastic and nanoplastic pollution, on cardiovascular health and provide an overview of the eco-disruptive causes of this pollution.

A study using advanced single-cell technologies has broadened our understanding of the diversity and complexity of brain endothelial cells by uncovering new endothelial subtypes and transcriptional patterns. These findings offer insights into potential therapeutic targets and emphasize the need for further research on vascular lineages and neurovascular interactions.

In this Review, the authors describe the bidirectional crosstalk between lysosome biology and immune cell function and polarization, focusing on immunometabolic reprogramming in the context of atherosclerosis and highlighting knowledge gaps and potential therapeutic strategies targeting immune cell lysosomes.

The gut microbiota has emerged as a risk factor that affects thrombotic phenotypes in several cardiovascular diseases. In this Review, Reinhardt and colleagues discuss the link between the gut microbiota, its metabolites and thromboembolic diseases, and summarize potential therapeutic interventions to modulate the gut microbiota.

Genetic testing for inherited cardiac disease has become part of routine clinical care. In this Review, Verdonschot et al. provide an overview of the reproductive options in the context of monogenic cardiac diseases, with a focus on preimplantation genetic testing, to prepare health-care professionals for discussions with their patients.

In this Review, Shi and co-workers summarize the available evidence on the role of eosinophils in cardiovascular diseases, highlighting differences between preclinical and clinical findings and placing clinical data in the context of experimental data to discuss potential pathogenic or protective roles of eosinophils in different cardiovascular disease settings.

The pathophysiology of heart failure with preserved ejection fraction (HFpEF) remains poorly understood. In this Review, Redfield and colleagues highlight the importance of studying human cardiac tissue in HFpEF, discuss sources, challenges and methods for studying human myocardial samples, summarize pathophysiological insights derived from studies of human myocardium in HFpEF and outline knowledge gaps to guide future research.

In this Review, Ghofrani and colleagues discuss the mechanisms underlying the development of pulmonary arterial hypertension, provide an overview of approved therapies and describe the predominantly non-vasodilatory drugs that are currently being tested in clinical trials.

Cardiovascular diseases are the leading cause of death in Latin America and the Caribbean (LAC), precipitated by the unique milieu of population growth, rapid urbanization, socioeconomic disparities and prevalent cardiometabolic risk factors. Brant and colleagues summarize trends in cardiometabolic health in LAC and discuss tailored, innovative solutions to address the growing burden of disease in the region.