Circulation Research

Mitochondrial heteroplasmy represents a fundamental determinant of mitochondrial function and disease, yet its consequences vary across different tissues. Although mitotic tissues possess mechanisms, such as cell division and mitochondrial turnover, to dilute or remove deleterious variants, postmitotic tissues lack this renewal capacity and are disproportionately vulnerable. Neuromuscular and neu…

Cardiovascular diseases remain the leading global cause of mortality, highlighting the need for improved early detection and targeted interventions. Extracellular vesicles (EVs) are nano-sized, bilipid-layered particles released by all cell types that carry RNAs, proteins, lipids, and metabolites reflective of their parent cells. They mediate intercellular communication by transferring cargo that…

Platelets are central to hemostasis and thrombosis. Excessive platelet activation contributes to arterial thrombotic events, including myocardial infarction, ischemic stroke, and complications of peripheral artery disease, whereas excessive platelet inhibition increases bleeding risk. Antiplatelet therapy remains a cornerstone of secondary prevention in atherosclerotic and thrombotic cardiovascul…

BACKGROUND: Anthracycline-induced cardiotoxicity (AIC) limits life-saving chemotherapy and is driven by early metabolic remodeling. The nuclear receptor ERRα (estrogen-related receptor α) is a master regulator of cardiac energy metabolism, but the temporal dynamics of its downregulation, its causal role in AIC pathogenesis, and whether it can be pharmacologically activated to confer protection re…

BACKGROUND: Recent studies have revealed heterogeneity among ribosomes. Pathological cardiac hypertrophy is characterized by profound alterations in translation. However, how ribosome heterogeneity contributes to this process remains largely unclear. METHODS: We used translating ribosome affinity purification coupled with mass spectrometry to profile ribosome-interacting proteins. Cardiomyocyte-s…

It is now apparent that cardiac form and function are governed at a system level by an integrated collective of heterogeneous single-cell programs that together regulate tissue homeostasis, drive disease emergence, and shape individualized responses to therapy. Current advances in single-cell proteomics and spatial multiomics by mass spectrometry imaging allow systematic dissection of clinically …

Recent advances in single-cell transcriptomics have revolutionized our understanding of cardiac development and maturation by resolving cellular heterogeneity, delineating lineage trajectories, and uncovering gene regulatory networks and intercellular signaling at unprecedented resolution. The heart develops through a tightly coordinated spatiotemporal process that extends from early organogenesi…

Cardiovascular function is tightly linked to tissue architectures, where the spatial organization of cells, extracellular matrix (ECM), vascular networks, and remodeling processes governs physiological performance and disease progression. Spatial proteomics has, therefore, emerged as a powerful framework for understanding cardiovascular biology and cardiovascular disease mechanisms by revealing s…

Skeletal muscle health and regeneration are highly orchestrated processes governed by a complex interplay of muscle stem cells, fibro-adipogenic progenitors, immune cells, and endothelial cells. Among these cell types, endothelial cells play a central role not only by regulating blood and nutrient flow to support metabolic and regenerative needs, but also by directly interacting with muscle stem …

BACKGROUND: Diabetic cardiomyopathy, a severe complication of diabetes, is marked by mitochondrial dysfunction, metabolic inflammation, and progressive cardiac impairment. Although STING (stimulator of interferon genes) is well recognized as a central mediator of innate immunity, its noncanonical role in metabolic regulation and mitochondrial dynamics in the diabetic heart remains largely unexplo…

BACKGROUND: Pulmonary hypertension (PH) is a progressive cardiopulmonary disorder characterized by vascular remodeling, abnormal vasoconstriction of small lung arteries, and right heart failure. Hypoxia causes vascular damage, leading to vessel stenosis or occlusion by aberrant endothelial cells, hypertrophy of the tunica media, and thrombus formation. But the precise molecular mechanisms underly…