bims-evecad 2025-12-21 papers

Issue of 2025–12–21
three papers selected by
Cliff Dominy

Cardiovasc Drugs Ther. 2025 Dec 18.

Extracellular Vesicles in Cardiac Cell Crosstalk: from Intercellular Communication to Clinical Translation.

Cardiovascular disease (CVD) remains a leading cause of morbidity and mortality globally, accounting for nearly one-third of deaths worldwide. Intercellular communication between cardiomyocytes and non-cardiomyocytes is fundamental to maintaining cardiac homeostasis and adapting to stress or injury. Among the mediators of this communication, extracellular vesicles (EVs) have emerged as pivotal regulators of cardiac function and remodelling, transporting bioactive molecules that reflect the state and origin of their parent cells. This review provides a systems-level synthesis of EV-mediated crosstalk in the heart, integrating evidence from cardiomyocyte- and non-cardiomyocyte-derived EVs, including fibroblast, endothelial, vascular smooth muscle, and immune cell sources. We discuss how these vesicles orchestrate signalling networks that influence cardiac remodelling, injury response, and disease progression. Distinct from prior reviews, our article extends beyond mechanistic summaries to explore the translational continuum of cardiac EVs-from their potential as diagnostic and prognostic biomarkers to emerging therapeutic and bioengineering strategies. Finally, we critically evaluate current technical and regulatory barriers impeding clinical translation, including isolation, characterisation, and validation challenges, and propose a forward-looking roadmap to advance EV-based diagnostics and therapeutics in cardiovascular medicine.

Keywords: Cardiac extracellular vesicles; Cardiac fibroblast EVs; Cardiac nonmyocytes; Cardiac pathophysiology; Cardiomyocytes; Cardiovascular diseases

DOI: https://doi.org/10.1007/s10557-025-07828-5

Clin Exp Nephrol. 2025 Dec 16.

Circulating small extracellular vesicles in chronic kidney disease and vascular calcification: "Tiny packages with big biological mission".

Shintaro Mandai.

Chronic kidney disease (CKD), a condition affecting over 850 million people worldwide, is a major global health issue. CKD leads to multimorbidities and disease complexity, expediting the aging process and increasing mortality rates-a phenomenon sometimes referred to as "renal senescence." The leading cause of death in patients with CKD is cardiovascular disease (CVD), accounting for one-third to one-half of all deaths, in stark contrast to cancer, which is the primary cause of death in the general population. While previous studies on kidney disease have focused extensively on urinary extracellular vesicles due to their potential as non-invasive diagnostic tools and their origin from kidney cells, our research highlighs the significance of circulating small extracellular vesicles (cEVs). We demonstrated that cEVs act as key mediators in the pathological intercellular and inter-organ communication between the kidneys and vascular smooth muscle cells (VSMCs). However, the biogenesis, cargo, and biological functions of cEVs remain incompletely understood under physiological and pathological conditions, including CKD. We identified microRNA (miRNA) transcriptomic signatures encapsulated in cEVs from CKD animal models, which were validated in human CKD samples. Notably, the depletion of specific miRNAs in CKD-derived cEVs promoted osteogenic differentiation of VSMCs and the deposition of calcium-phosphate crystals in vessels. In contrast, miRNAs enriched in cEVs from healthy individuals suppress these pathological processes, acting as a safeguard. These findings and future research could pave the way for the development of diagnostic and therapeutic platforms leveraging cEVs in nephrology.

Keywords: Chronic kidney disease; Inter-organ communication; Renal senescence; Small extracellular vesicles; Vascular calcification

DOI: https://doi.org/10.1007/s10157-025-02793-7

Free Radic Biol Med. 2025 Dec 15. pii: S0891-5849(25)01432-7. [Epub ahead of print]

Adipocyte Extracellular Vesicle Mitochondrial Cargo is Linked to Cardiomyocyte Dysfunction in Type 2 Diabetes-Related Heart Failure with Preserved Ejection Fraction.

Haibin Ji, Tian Cao, Zixuan Tan, Rui Zheng, Jinhui Bian, Wenfeng Lin, Chunze Yuan, Yongfeng Shao, Hongyan Li, Junjie Du.

Heart failure with preserved ejection fraction (HFpEF) is increasingly prevalent in type 2 diabetes (T2D), yet disease-modifying therapies remain limited. Here we identify an adipose-cardiac communication axis in which stressed adipocytes export extracellular vesicles (AdEVs) laden with oxidatively damaged mitochondrial proteins that are associated with impaired cardiomyocyte bioenergetics and increased apoptosis. Single-nucleus RNA-seq of human subcutaneous adipose tissue from patients with T2D-HFpEF revealed metabolic stress in adipocytes, characterized by enriched mitochondrial oxidative stress genes and reduced metabolic flux. The severely affected AD3 subpopulation exhibits mitochondrial impairments, potentially accompanied by increased AdEV release. In parallel, circulating AdEVs were elevated and their mitochondrial cargo showed greater oxidative modification; AdEV abundance tracked systemic protein carbonyls and clinical markers of cardiac load. In vitro, lipotoxic adipocytes released AdEVs enriched for mitochondrial components with increased protein carbonylation. When applied to human cardiomyocytes (AC16 and human induced pluripotent stem cell-derived cardiomyocytes), these AdEVs increased reactive oxygen species (ROS), dissipated mitochondrial membrane potential, fragmented mitochondrial networks, reduced oxygen consumption and ATP production, and activated intrinsic apoptosis and heart-failure marker expression. Inhibition of EV biogenesis (GW4869) or scavenging of mitochondrial ROS (Mito-TEMPO) blunted these effects. Collectively, our data support a model in which oxidatively modified mitochondrial cargo within AdEVs links adipose stress to cardiomyocyte dysfunction in T2D-HFpEF and suggest that AdEV release and mitochondrial ROS may represent tractable therapeutic targets.

Keywords: Heart failure with preserved ejection fraction; adipocyte-derived extracellular vesicles; adipose single-nucleus profiling,cardiomyocytes; apoptosis; intercellular signaling; mitochondrial dysfunction; oxidative stress; type 2 diabetes mellitus

DOI: https://doi.org/10.1016/j.freeradbiomed.2025.12.016