bims-evecad 2026-02-22 papers

Issue of 2026–02–22
three papers selected by
Cliff Dominy

Sci Bull (Beijing). 2026 Jan 30. pii: S2095-9273(26)00111-8. [Epub ahead of print]

Bioengineering extracellular vesicles for enhanced therapeutic functionality and clinical potential in the cardiovascular system.

Yongtao Wang, Meiyu Hu, Michail Spanos, Shihui Xu, Jiaxin Song, Guoping Li, Dragos Cretoiu, Junjie Xiao.

Cardiovascular diseases (CVDs) are a leading cause of morbidity, disability, and mortality worldwide, posing a significant threat to global health. These diseases include myocardial infarction (MI), heart failure (HF), hypertension, atherosclerosis (AS), and other pathological cardiac disorders. Despite notable advances in CVD management, such as cardiac-targeted pharmacotherapies, interventional procedures, and heart transplantation, major challenges persist, including adverse drug effects, postoperative complications, and the persistent shortage of heart donors. Extracellular vesicles (EVs) have recently emerged as a promising therapeutic modality owing to their high delivery efficiency, precise targeting potential, and capacity to promote cardiac repair and regeneration. EVs carry a diverse repertoire of bioactive cargos, including proteins, nucleic acids, lipids, and metabolites, facilitating intercellular regulation of immune response, tissue repair, and regenerative processes. Advances in bioengineered EVs also develop the therapeutic potential by enabling the design of vesicles with enhanced targeting specificity and controlled cargo delivery. This review summarizes the complex interactions between EVs and the cardiovascular system, with particular emphasis on their roles in cellular communication, microenvironment modulation, and immune regulation. We further highlight the regenerative capacity of EVs in cardiovascular repair, and discuss emerging clinical applications of native and bioengineered EVs in cardiovascular homeostasis, remodeling, metabolism, and regeneration. These insights pave the way for further exploration of bioengineered EVs as a novel therapeutic platform in cardiovascular medicine.

Keywords: Bioengineered EVs; Cardiovascular diseases (CVDs); Extracellular vesicles (EVs); Heart failure (HF); Myocardial infarction (MI); Targeted drug delivery

DOI: https://doi.org/10.1016/j.scib.2026.01.067

Biochim Biophys Acta Gen Subj. 2026 Feb 12. pii: S0304-4165(26)00012-7. [Epub ahead of print] 130912

Cardiac extracellular vesicles aggravate cardiomyocyte ferroptosis in myocardial ischemia-reperfusion injury via miR-155-5p-Nfe2l2 signaling.

Xinyu Ge, Qingshu Meng, Jing Liu, Enhao Wang, Xuan Liu, Shanshan Shi, Xin Gong, Zhongmin Liu, Wei Han, Xiaohui Zhou.

BACKGROUND: Ischemia-reperfusion (IR) injury represents a major cause of cell death post myocardial infarction. Ferroptosis is a newly discovered form of regulated cell death (RCD) dependent on iron and reactive oxygen species (ROS). We recently confirmed that cardiac IR triggers the increased release of extracellular vesicles (EVs) which aggravates cardiac dysfunction. Whether and how these EVs contribute to cardiac ferroptosis during myocardial IR injury remain elusive.
METHODS: Murine myocardial IR models were established by ligation of the left anterior descending coronary artery for 45 min and then reperfusion. Then EVs from the heart subjected to IR (IR-EVs) were isolated. We further confirmed the effect of IR-EVs on cardiomyocyte ferroptosis at the cellular and animal levels using methods such as qPCR, WB, and miRNA sequencing.
RESULTS: Adoptive transfer of IR-EVs and EVs inhibition experiments confirmed that IR-EVs act as a vital factor that contributes to the cardiomyocyte ferroptosis during cardiac IR, with increased Ptgs2 expression and malondialdehyde (MDA) production, as well as decreased NADPH level. Moreover, miR-155-5p enriched in IR-EVs can be delivered into cardiomyocytes and promoted the ferroptosis of cardiomyocytes in the peroxidation injury. Nfe2l2 was further confirmed as the target gene of miR-155-5p by luciferase reporter assay. Consistently, molecules targeting Nfe2l2 modulated the H2O2 or oxygen glucose deprivation/reoxygenation (OGD/R) induced ferroptosis, involving the downstream antioxidant response elements (AREs) of the Nfe2l2 pathway including Nqo1, HO1, Fth1, and Slc7a11.
CONCLUSION: The present results provided a novel EV-based ferroptosis regulation mechanism in cardiac IR injury. Strategies targeting the IR-EVs-miR-155-5p-Nfe2l2 axis may be of therapeutic potential to prevent cardiac ferroptosis and dysfunction after myocardial IR.

Keywords: Extracellular vesicles; Ferroptosis; Myocardial ischemia-reperfusion injury; Nfe2l2; miRNA

DOI: https://doi.org/10.1016/j.bbagen.2026.130912

Clin Exp Hypertens. 2026 Dec 31. 48(1): 2631601

AMPK-dependent maturation of hiPSC-derived cardiomyocytes induced by human cardiac fibroblast exosomes.

Kele Qin, Xiuneng Li, Xun Wu, Xiaohui Xie, Kun Xiang, Huatao Zhou, Jinfu Yang, Chengming Fan.

BACKGROUND: Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) are a promising therapy for ischemic cardiomyopathy, which is often secondary to hypertension but remain functionally immature. We investigated whether exosomes from human cardiac fibroblasts (hc-FB-EXOs) promote hiPSC-CMs maturation and improve their reparative efficacy after myocardial infarction (MI).
METHODS: hc-FB-EXOs were isolated from cultured fibroblasts. hiPSC-CMs were treated with hc-FB-EXOs or vehicle and assessed for morphology, sarcomeric organization, metabolism, and electrophysiology. RNA sequencing and Western blotting were used to explore mechanisms. In a mouse MI model, left ventricular function, infarct size, wall thickness, and graft density were evaluated after intramyocardial injection of hiPSC-CMs with or without hc-FB-EXOs.
RESULTS: hc-FB-EXOs induced adult-like features in hiPSC-CMs, including increased cell size and sarcomere length, fetal-to-adult isoform switching of myosin and troponin, enhanced mitochondrial respiration, and a shift toward fatty acid-based oxidative metabolism. Electrophysiological maturation was evidenced by a higher peak sodium current density, faster upstroke velocity, and more mature action potential and field potential profiles. Transcriptomic and biochemical analyses identified activation of AMP-activated protein kinase (AMPK) signaling, with the modulation of downstream regulators of fatty acid oxidation. In vivo, co-delivery of hc-FB-EXOs with hiPSC-CMs improved the left ventricular ejection fraction, reduced the infarct size, and increased the graft density compared with those of hiPSC-CMs alone.
CONCLUSION: hc-FB-EXOs promote the maturation of hiPSC-CMs via AMPK-mediated metabolic reprogramming and enhance their therapeutic benefit after MI. Cardiac fibroblast-derived exosomes may serve as a practical adjunct to optimize hiPSC-CMs-based therapy for ischemic cardiomyopathy.

Keywords: AMPK; Human induced-pluripotent stem cell derived cardiomyocytes; cardiac fibroblast; exosome; maturation

DOI: https://doi.org/10.1080/10641963.2026.2631601