bims-evecad 2026-06-07 papers

Issue of 2026–06–07
six papers selected by
Cliff Dominy

Eur Heart J. 2026 Jun 05. pii: ehag404. [Epub ahead of print]

Extracellular vesicles in atherosclerotic cardiovascular disease: mechanisms and therapeutic implications.

Nicolas Amabile, Elena Aikawa, Françoise Dignat-George, Chantal M Boulanger, Yao Yao, Aurélie S Leroyer.

Extracellular vesicles (EVs) have emerged as central regulators of intercellular communication in cardiovascular pathology. In atherosclerosis, EVs derived from endothelial, leukocytes, platelets, erythrocytes, and vascular smooth muscle cells (VSMCs) actively participate in the initiation and progression of arterial wall inflammation. Endothelial-derived EVs can carry pro-inflammatory proteins and microRNAs that impair endothelial function, promote leukocyte adhesion, and enhance oxidative stress, thereby facilitating early lesion formation. Platelet- and leukocyte-derived EVs further amplify these processes by stimulating monocyte recruitment, cytokine release, and thrombotic signalling within the developing plaque. As atherosclerotic lesions mature, EVs contribute to key cellular phenotypes, including macrophage foam cell formation and VSMC switching towards synthetic or osteogenic states. These vesicles transport bioactive lipids, enzymes, and nucleic acids that influence cholesterol handling, extracellular matrix remodelling, and apoptotic signalling, ultimately contributing to plaque instability. EVs are also critical drivers of vascular calcification, a hallmark of advanced atherosclerosis. VSMC- and macrophage-derived EVs can serve as nucleation sites for hydroxyapatite deposition, particularly when enriched with phosphatidylserine, annexins, or calcification-regulatory microRNAs. Dysregulated mineral metabolism, oxidative stress, and inflammation further modify EV cargo in ways that favour calcifying microenvironments. As these microcalcifications coalesce, they increase arterial stiffness but also contribute to plaque instability. Given their accessibility in circulation and their mechanistic involvement, EVs offer promising opportunities as biomarkers for monitoring atherosclerosis development, as well as therapeutic targets. Modulating EV release, modifying their composition, or engineering EV-based delivery systems represents an innovative frontier for future therapeutic strategies in atherosclerotic disease.

Keywords: Atherosclerosis; Extracellular vesicles; Thrombosis; Vascular calcifications

DOI: https://doi.org/10.1093/eurheartj/ehag404

J Nanobiotechnology. 2026 Jun 04.

M2 microglia-derived migrasome-enriched extracellular vesicles restore mitochondrial homeostasis to orchestrate neurovascular unit recovery after ischemic stroke.

Yuanjia Zhang, Jie Wu, Leyi Liu, Yiqian Zhu, Jierui Zhang, Jinghong Xu, Xuefeng Shi, Yu Yu, Chao Wang, Jiajing Xiao, Xuanchenye Zhang, Zhaorong Li, Wenqi Huang, Wenzhi Li, Zhongxing Wang, Tingting Li.

Ischemic stroke is a major cause of disability with few treatment options available. Microglia-driven neuroinflammation contributes significantly to stroke pathology, and promoting anti-inflammatory microglial phenotypes represents a promising strategy. Migrasomes are newly discovered organelles mediating intercellular communication, yet their role in ischemic stroke remains unexplored. This study demonstrates that M2 microglia-derived migrasome-enriched extracellular vesicles (EVs) exert potent neuroprotection in both OGD/R cell models and MCAO mice. These migrasome-enriched EVs were efficiently internalized by microglia, astrocytes, neurons, and microvascular endothelial cells, promoting microglial M2 polarization, suppressing astrocytic aberrant activation, reducing neuronal apoptosis, and enhancing angiogenesis. Intracerebral administration of M2 microglia-derived migrasome-enriched EVs significantly reduced infarct volume, ameliorated cerebral edema, improved cerebral blood flow, and accelerated neurological and cognitive recovery without detectable toxicity. Mechanistically, migrasome-enriched EVs activated the cAMP/EPAC1/Rap1 signaling pathway in microglia, leading to restored mitochondrial homeostasis. Collectively, these findings identify M2 microglia-derived migrasome-enriched EVs as novel intercellular messengers that orchestrate neurovascular unit recovery after ischemic stroke, positioning migrasome-enriched EVs as promising candidates for stroke therapy.

Keywords: Ischemic stroke; Microglia polarization; Migrasome-enriched extracellular vesicles; Mitochondrial homeostasis; Neurovascular unit recovery

DOI: https://doi.org/10.1186/s12951-026-04643-4

Int J Nanomedicine. 2026 ;21 594815

Plant-Derived Extracellular Vesicles for Nanomedicine in Cardiopulmonary Diseases: A Narrative Review.

Juan-Juan Zhang, Yu-Qian Huang, Xuekai Liu, Ping Xie.

This narrative review summarizes research progress on plant-derived extracellular vesicles (PEVs) for nanomedicine in cardiopulmonary system diseases, based on key literature covering isolation, engineering, and disease mechanisms. PEVs possess high biocompatibility, low immunogenicity, broad source availability, and scalability. Their bioactive cargo (proteins, nucleic acids, lipids, secondary metabolites) regulates inflammation, oxidative stress, apoptosis, and fibrosis. This review systematically discusses PEV characteristics, large-scale isolation, and engineering approaches, with a focus on multi-target and cell-specific mechanisms in atherosclerosis, myocardial infarction, COPD, and pulmonary fibrosis. Although challenges in standardization, in vivo mechanisms, and translation remain, engineered PEVs hold promise as efficient and safe nanomedicines. The unique contribution of this review is to integrate PEV preparation and engineering with their disease-specific mechanisms, providing a coherent framework for future translational research in cardiopulmonary nanomedicine.

Keywords: cardiovascular diseases; drug delivery; nanomedicine; plant-derived extracellular vesicles; respiratory system diseases

DOI: https://doi.org/10.2147/IJN.S594815

Front Pharmacol. 2026 ;17 1870690

Editorial: Epigenetic modifications and cardiovascular diseases.

Indira Pokkunuri, Cerrone R Foster, Suman Dalal.

Keywords: DNA methylation; cardiovascular diseases; epigenetics; extracellular vesicles; vascular remodeling

DOI: https://doi.org/10.3389/fphar.2026.1870690

Mater Today Bio. 2026 Jun;38 103236

Epicardial extracellular vesicles modulate gene expression following ischemia-reperfusion injury in heart-on-a-chip.

Karl T Wagner, Dawn Bannerman, Qinghua Wu, Simon Pascual-Gil, Ian Fernandes, Luis Felipe Jiménez Vargas, Shuo Yan, Ramak Khosravi, Sargol Okhovatian, Dhana Abdo, Milica Radisic.

The epicardium is an essential regulator of cardiac development, homeostasis, and injury, yet the composition and impacts of epicardial cell-secreted extracellular vesicles (EVs) remain incompletely understood. Here, we harness an epicardial Biowire platform integrating human stem cell derived epicardial cells with functional myocardium and apply transcriptomics to reveal enriched EV transport in tissues containing epicardial cells. Profiling epicardial-EVs identified key miRNAs and their conservation through stimulated epithelial-to-mesenchymal transition. Supplementation of epicardial-EVs to tissues undergoing ischemia-reperfusion injury influenced gene expression associated with reduction of extracellular matrix remodeling, fibroblast activation, and suppression of cell-ECM interactions. Correlation of EV-miRNAs with mRNA targets highlighted the role of miR-30d-5p, miR-9-5p, miR-16-5p, and the let-7 family in moderating deleterious fibrotic activation and matrix remodeling during myocardial injury in vitro.

Keywords: Cardiac tissue engineering; Epicardium; Extracellular vesicles; Heart-on-a-chip; Ischemia-reperfusion injury

DOI: https://doi.org/10.1016/j.mtbio.2026.103236

Circ Res. 2026 Jun 05. 138(12): e327471

Cardiac Lipid Metabolism: Cells, Metabolites, and Rhythms.

Ira J Goldberg, Martin E Young, P Christian Schulze, Konstantinos Drosatos.

Although studied for decades, metabolic therapies that target cardiac lipid metabolism are underdeveloped, and most approaches have thus far failed as a heart failure treatment. In contrast, new therapies for diabetes and obesity are widely used for the prevention and treatment of heart failure. The heart depends heavily on lipid uptake and utilization for proper function. Too much or too little cardiac lipid catabolism becomes detrimental and causes heart failure, either due to lipotoxicity or energetic depletion. For this reason, cardiac lipid metabolism is carefully controlled and balanced. Moreover, cardiac fatty acid oxidation affects systemic energy metabolism, as evidenced by changes in circulating levels of fatty acids and lipoproteins. This review describes mechanisms of regulation of lipid uptake and metabolism by cardiomyocytes, how fatty acid and glucose use are coordinated, how mitochondrial fatty acid metabolism is regulated at the transcriptional and posttranslational levels, as well as how fed/fasting cycles and circadian clocks modulate heart metabolism during the day. We review studies that used cultured cells, animal models, human tissue, and nuclear tracing. Our objective is to present current knowledge on mechanisms that control cardiac lipid metabolism, thereby suggesting experimental directions that could lead to new metabolic therapies.

Keywords: fatty acids; glucose; heart failure; lipoproteins

DOI: https://doi.org/10.1161/CIRCRESAHA.126.327471