Reviews & Analysis

The eye and the brain are both recognized as immune-privileged sites. Research now indicates that responses in the eye mirror those in the central nervous system (CNS), offering major implications for the treatment of CNS cancers and infections.

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.

High-throughput sequencing technologies have revolutionized the study of transcription across cell types and many biological phenomena. Brash et al. have developed a resource based on 240 endothelial bulk RNA-sequencing datasets that uses machine learning to predict whether a gene is the product of leaky or active transcription.

Acute depletion of meningeal lymphatic vessels impairs the clearance of cerebrospinal fluid and brain macromolecules. A new study by Antila et al. shows that amyloid pathology in Alzheimer’s disease is neither improved nor aggravated by genetic expansion or depletion of meningeal lymphatic vessels.

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

Hepatocytes are recognized as having a primary role in production and clearance of apolipoprotein B100-containing lipoproteins. A new study finds that Kupffer cells can respond to the initial atherogenic dyslipidemia and regulate levels of circulating lipoprotein.

Older men with loss of the Y chromosome are more susceptible to heart failure but the responsible genes have not been identified. A study now shows that loss of a single Y chromosome gene in bone marrow cells induces heart failure by switching cardiac macrophages from an inflammatory to a fibrogenic pattern of gene activity.

Recent analyses of observational data from 340,000 UK Biobank participants indicate that people with a higher biological age than their same-aged peers have an increased risk of developing cardiometabolic diseases. By contrast, the ability of accelerated biological aging to predict multimorbidity progression is relatively limited.

Myocarditis, an inflammatory heart disease, causes cardiomyocyte loss leading to heart failure. Research now shows that BMP4 is crucial for cardiac tissue homeostasis, and targeted neutralization of BMP inhibitors GREM1 and GREM2 mitigates T cell-induced myocardial inflammation and maintains cardiomyocyte integrity.

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.

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.

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.