bims-evecad 2026-08-02 papers

bims-evecad

Biomed News

on Extracellular vesicles and cardiovascular disease

Issue of 2026–08–02
ten papers selected by
Cliff Dominy

Bioengineering Approaches for Nanomedicine Delivery in Therapy of Myocardial Infarction.
Extracellular vesicles: a common mechanism for remote ischemic preconditioning and exercise-induced cardioprotection?
Implantable Microsphere-Mediated Targeted Delivery of Mesenchymal Stem Cell-Derived Extracellular Vesicles Attenuates Neuroinflammation and Promotes Recovery After Cerebral Ischemia.
Exercise rejuvenates the "muscle-heart" crosstalk: skeletal muscle-derived exosomal miRNAs in cardiac aging.
Cardiomyocyte-macrophage cross-talk reduces doxorubicin cardiotoxicity by polarizing macrophages via EV miR-142-3p/135a-5p.
Cell Therapy as Metabolic Rescue after Ischemic Stroke: Rewiring Bioenergetics, Redox Homeostasis, and Neurovascular Repair.
Extracellular Vesicle-Associated microRNAs as Candidate Biomarkers and Mediators of Diabetic Complications: Clinical and Translational Evidence Across Neuropathy, Diabetic Kidney Disease, Retinopathy, and MASLD.
[Research progress on extracellular vesicles in aortic aneurysms].
Extracellular vesicle-mediated immunity-coagulation interaction in cancer-associated thrombosis during the immunotherapy era.
Thrombin reprograms endothelial extracellular vesicles.

Arterioscler Thromb Vasc Biol. 2026 Jul 30.

Bioengineering Approaches for Nanomedicine Delivery in Therapy of Myocardial Infarction.

Jiawen Zou, Dashuai Zhu, Xiao Cheng, Ke Cheng.

  Cardiovascular disease remains the leading cause of death globally. In particular, ischemic heart disease represents the most common condition in clinics. Adult hearts have minimal regenerative capacity. Upon myocardial infarction, the formation of activated myofibroblasts replaces the massive loss of cardiomyocytes. Nanomedicine has emerged as a promising strategy for cardiovascular disease treatment, with synthetic nanoparticles and extracellular vesicles serving as representative delivery platforms. However, directly applying these nanomedicines faces several challenges, including insufficient cardiac targeting, poor retention rate at the injured site, and potential biocompatibility concerns. To overcome these limitations, different bioengineering approaches have been adopted. In this review, we discussed the landscape of cardiovascular nanomedicine, encompassing both synthetic nanocarriers and biological carriers and targeted delivery. We further evaluated the engineering approaches to enhance carrier performance. Multiple administration routes are also compared. Collectively, these advances represent a shift toward an integrated, multifunctional delivery platform with the potential to translate cardiac nanomedicine from bench to bedside.

Keywords:  blood pressure; cardiovascular diseases; drug liberation; heart rate; lipid nanoparticles

DOI:  https://doi.org/10.1161/ATVBAHA.126.324247
Am J Physiol Heart Circ Physiol. 2026 Jul 30.

Extracellular vesicles: a common mechanism for remote ischemic preconditioning and exercise-induced cardioprotection?

Sean M Davidson.



Keywords:  extracellular vesicles; heart; ischemia; reperfusion

DOI:  https://doi.org/10.1152/ajpheart.00569.2026
Front Biosci (Landmark Ed). 2026 Jul 24. 31(7): 52994

Implantable Microsphere-Mediated Targeted Delivery of Mesenchymal Stem Cell-Derived Extracellular Vesicles Attenuates Neuroinflammation and Promotes Recovery After Cerebral Ischemia.

Yiran Wang, Xiaorui Lei, Xiao Liang, Yiwen Huang, Xin Zhang, Tian Tian.

   BACKGROUND: Ischemic stroke is a major cause of death and disability, in which neuroinflammation exacerbates injury. Mesenchymal stem cell (MSC)-derived extracellular vesicles (EVs) offer therapeutic potential but face translational hurdles in scalable production, rapid systemic clearance, and inefficient targeted delivery.
METHODS: We engineered an implantable alginate-microsphere system encapsulating EV-secreting MSCs and displaying the RGD-4C peptide (ACDCRGDCFC) on its surface. This platform functions as a bioreactor that sustains the release of functionalized EVs with enhanced targeting to the ischemic brain. Proteomics analyses compared EVs derived from 3D-microsphere cultures and conventional 2D cultures. Efficacy was evaluated in a mouse stroke model with intraperitoneal microsphere implantation, assessing biodistribution, neuroinflammation, microglial polarization, and recovery.
RESULTS: The system sustained the release of targeted EVs, demonstrating proteomic enrichment of anti-inflammatory cargo. In vivo, the platform enhanced EV accumulation in the ischemic brain, reduced neuroinflammation, shifted microglia toward a reparative phenotype, and significantly improved neuronal survival and functional recovery.
CONCLUSION: This integrated platform represents a promising preclinical strategy for treating ischemic stroke and has potential applications in other neuroinflammatory diseases. This system circumvents the need for EV extraction and storage while eliminating the peak-and-trough kinetics of bolus injections, and suggests potential for future translation pending further validation.

Keywords:  alginate microspheres; extracellular vesicles; ischemic stroke; mesenchymal stem cells; neuroinflammation

DOI:  https://doi.org/10.31083/FBL52994
Front Cardiovasc Med. 2026 ;13 1863985

Exercise rejuvenates the "muscle-heart" crosstalk: skeletal muscle-derived exosomal miRNAs in cardiac aging.

Ruibin Jing, Xue Pang, Xiaona Zhu, Sibao Huang, Xing Gao.

  The deleterious intersection of sarcopenia and age-related heart failure represents a profound global health challenge. While skeletal muscle is increasingly recognized as a major endocrine hub, cannot fully account for the persistent epigenetic changes in the aged myocardium. This points to a key mechanistic gap in the "muscle-heart" inter-organ crosstalk. Following PRISMA guidelines, this systematic review (incorporating 51 rigorous in vivo and clinical studies) maps the bimodal skeletal muscle-derived extracellular vesicle (SkM-EV) and microRNA (miRNA) axis in cardiac aging. We delineate a pathological baseline where aging and sarcopenia trigger the release of senescence-associated extracellular vesicles (EVs). These toxic vesicular payloads actively propagate myocardial inflammaging, structural remodeling, and apoptosis. Conversely, regular exercise rejuvenates by this network via an epigenetic mechanism. Mechanical loading stimulates the systemic release of "exerkines"-exercise-conditioned EVs enriched with potent cardioprotective myomiRs (e.g., miR-1, miR-133a, miR-342-5p). By systematically categorizing these findings from single-molecule downstream targets (anti-apoptosis, anti-fibrosis) to macroscopic poly-pathway synergy (antioxidant and metabolic reprogramming), we construct a comprehensive molecular roadmap of EV-mediated myocardial rejuvenation. Ultimately, deciphering this vesicular signaling network will elucidate the fundamental epigenetic mechanisms underlying "exercise as medicine," and paves the way for novel translational horizons. We propose that targeting the bimodal SkM-EV axis will accelerate the development of EV-based liquid biopsies for sarcopenic cardiomyopathy and pioneer cell-free "exercise mimetics" for frail, exercise-intolerant aging populations.

Keywords:  cardiac aging; exercise mimetics; exerkines; extracellular vesicles (Exosomes); microRNAs (myomiRs); sarcopenia; skeletal muscle-Heart crosstalk

DOI:  https://doi.org/10.3389/fcvm.2026.1863985
iScience. 2026 Aug 21. 29(8): 116787

Cardiomyocyte-macrophage cross-talk reduces doxorubicin cardiotoxicity by polarizing macrophages via EV miR-142-3p/135a-5p.

Xiyuan Chen, Tingting Chen, Yuxin Hu, Anlan Wang, Tongtong Yu, Huating Xie, Yafei Hu, Yongyu Wang, Guoquan Pan, Shengwei Jin, Ming Li.

  Doxorubicin (DOX) cardiotoxicity (DiCM) is mediated by macrophages. c-Kit inhibition drives M2 macrophage polarization, and emerging evidence suggests that cardiomyocyte-derived extracellular vesicles (CM-EVs) participate in immune modulation during cardiac injury. Building on these observations, we hypothesized that cardiomyocyte-specific c-Kit mutation (Tg-Wv) protects against DiCM by altering EV-mediated cardiomyocyte-macrophage crosstalk. In DiCM models, Tg-Wv mice exhibited improved survival, reduced cardiac atrophy, and enhanced function, with a shift toward CD163+ M2 anti-inflammatory macrophages, a higher M2/M1 ratio, and diminished tissue damage, oxidative stress, and apoptosis. CM-EVs reporter mice showed real-time uptake by cardiac macrophages. Micro RNA (miRNA) sequencing identified upregulated miR-142-3p and miR-135a-5p in Tg-Wv cardiomyocytes and EVs. Cardiac macrophages displayed reduced HIF-1α and elevated Arg-1. Transfection of these miRNAs induced CD163+ M2-like polarization in vitro. Our findings demonstrate that cardiomyocyte c-Kit mutation enriches miR-142-3p and miR-135a-5p in EVs, which suppress HIF-1α and promote protective M2-like macrophage polarization, unveiling a novel EV-mediated cardioprotective pathway.

Keywords:  cardiotoxicity; doxorubicin; extracellular vesicles; macrophages; miR-142-3p and miR-135a-5p

DOI:  https://doi.org/10.1016/j.isci.2026.116787
Stem Cell Rev Rep. 2026 Jul 28.

Cell Therapy as Metabolic Rescue after Ischemic Stroke: Rewiring Bioenergetics, Redox Homeostasis, and Neurovascular Repair.

Salar Bakhtiyari, Iraj Alipourfard.

  Ischemic stroke represents a dynamic metabolic disorder of the neurovascular unit (NVU) rather than a static vascular occlusion followed by neuronal demise. Immediate oxygen and glucose deprivation rapidly deplete ATP, disrupt the transmembrane ionic gradients, increase glutamate excitotoxicity, and overload mitochondrial with calcium. These events alter glycolytic, lipid, amino acid, and redox pathways. During the subacute and chronic phases, astrocytes, microglia, macrophages, endothelial cells, pericytes, oligodendrocytes, and surviving neurons continue to remodel substrate utilization. These phase-specific metabolic programs either accelerate infarct expansion and blood-brain barrier disruption or facilitate angiogenesis, synaptic plasticity, and tissue repair. Consequently, cell-based therapeutic paradigms have shifted from direct neuronal replacement toward metabolic rescue. Transplanted cells and cell-free derivatives deliver trophic factors, extracellular vesicles, microRNAs, antioxidant signals, mitochondrial cues, and immunoregulatory factors. These signals enhance mitochondrial fitness, restore redox homeostasis, attenuate pro-inflammatory glycolysis, and stabilize endothelial-pericyte coupling to stabilize a permissive neurorehabilitation microenvironment. This review synthesizes post-stroke metabolic landscapes and evaluates how mesenchymal stromal, neural stem/progenitor, endothelial progenitor, cord blood-derived, and mononuclear cells, and extracellular vesicles, may be incorporated into a phase-specific translational framework supported by target-engagement biomarkers and standardized potency assays.

Keywords:  Blood-brain barrier; Cell therapy; Extracellular vesicles; Glycolysis; Ischemic stroke; Lactate; Mesenchymal stromal cells; Metabolic reprogramming; Mitochondria; Neurovascular unit; Oxidative stress

DOI:  https://doi.org/10.1007/s12015-026-11200-x
Metabolites. 2026 Jul 16. pii: 500. [Epub ahead of print]16(7):

Extracellular Vesicle-Associated microRNAs as Candidate Biomarkers and Mediators of Diabetic Complications: Clinical and Translational Evidence Across Neuropathy, Diabetic Kidney Disease, Retinopathy, and MASLD.

Raúl Ibarra-Salce, José Luis Eduardo Doval-Caballero, Daniel Uribe-Cortés, Genesis Dinora Eugenio-Ponce, Mariela Ibarra-Salce, Omar Jaime-Leal, Manuel Ramón García-Sáenz.

   BACKGROUND/OBJECTIVES: Type 2 diabetes is increasingly recognized as a systemic disorder driven not only by chronic hyperglycemia and insulin resistance, but also by dysregulated interorgan communication. Extracellular vesicles (EVs), including exosomes and microvesicles, have emerged as biologically active carriers of proteins, lipids, and microRNAs capable of modulating gene expression in recipient cells. This narrative review integrates clinical, experimental, and translational evidence on EV-associated microRNAs as candidate biomarkers and potential mediators of diabetic complications, with emphasis on diabetic neuropathy, diabetic kidney disease, diabetic retinopathy, and metabolic dysfunction-associated steatotic liver disease (MASLD).
METHODS: This review was aligned with the SANRA framework and focused on biological plausibility, evidence from tissue and biofluids, biomarker potential, therapeutic implications, and barriers to clinical translation. Studies were additionally interpreted according to biological matrix, EV-carrier specificity, analytical platform, study design, and level of functional validation.
RESULTS: Across complications, EV-associated microRNAs appear to participate in shared pathogenic processes, including oxidative stress, inflammation, endothelial dysfunction, fibrosis, angiogenesis, neurodegeneration, and metabolic memory. In diabetic neuropathy, microRNAs such as miR-146a, miR-155, miR-21-5p, and miR-148a-3p have been linked to neuroinflammation, Schwann-cell dysfunction, axonal injury, and neuropathic pain. In diabetic kidney disease, miR-21, miR-29, miR-30, and miR-126 are implicated in podocyte injury, tubulointerstitial fibrosis, albuminuria, and microvascular dysfunction. In diabetic retinopathy, microRNAs including miR-146a, miR-155, miR-21, miR-126, and miR-200b contribute to neurovascular injury, inflammation, barrier disruption, and angiogenesis. In MASLD associated with diabetes, hepatocyte-derived EVs carrying microRNAs such as miR-1 and miR-126a-3p may link hepatic lipotoxicity to endothelial inflammatory and β-cell dysfunction.
CONCLUSIONS: Although EV-associated microRNAs offer promising opportunities for biomarker discovery, risk stratification, and targeted therapies, clinical translation remains limited by heterogeneity in EV isolation, microRNA quantification, biological matrices, and outcome definitions. Distinguishing EV-associated miRNAs from total circulating extracellular miRNAs remains essential for biological interpretation. Standardized, longitudinal, and externally validated studies are required before these signals can be implemented as actionable tools in precision diabetes care.

Keywords:  MASLD; biomarkers; diabetic kidney disease; diabetic neuropathy; diabetic retinopathy; extracellular vesicles; microRNAs; type 2 diabetes

DOI:  https://doi.org/10.3390/metabo16070500
Sheng Wu Gong Cheng Xue Bao. 2026 Jul 25. pii: 1000-3061(2026)07-2927-16. [Epub ahead of print]42(7): 2927-2942

[Research progress on extracellular vesicles in aortic aneurysms].

Zongyou Xie, Lianglin Wu, Huibo Ma, Yuehong Zheng, Jianqiang Wu, Zairong Wei.

  Aortic aneurysms, including thoracic aortic aneurysms (TAA) and abdominal aortic aneurysms (AAA), represent a group of severe vascular lesions with insidious onset and high mortality. Currently, effective diagnostic markers and pharmacological interventions remain lacking in clinical practice. Extracellular vesicles (EVs), as key mediators of intercellular communication, have attracted increasing attention in the research on aortic aneurysms due to their high content of bioactive molecules, favorable biocompatibility, low immunogenicity, and inherent targeting capacity. This review systematically elaborated on the research progress on EVs in TAA and AAA, highlighting their significant role in the development and progression of aortic aneurysms. EVs play a crucial role by mediating core pathological processes, including endothelial dysfunction, phenotypic transformation of vascular smooth muscle cells, inflammatory immune responses, and extracellular matrix remodeling. Additionally, this review discussed the potential of disease-specific molecules carried by EVs as novel liquid biopsy markers for the early diagnosis of aortic aneurysms. Furthermore, this review evaluated the application prospects of EVs as natural drug delivery platforms and EV-based therapeutic strategies for aortic aneurysm through engineering modifications (such as targeting peptide modification and biomaterial integration). In particular, "cell-free" immunomodulatory therapies, which enhance targeting capacity to lesion sites through engineering modifications and focus strategically on regulating the phenotype and function of key immune cells (such as macrophages), are increasingly emerging as a cutting-edge direction with the greatest translational potential in this field. Despite challenges such as targeted delivery, the integration of engineering technologies with nanomedicine holds promise for opening new avenues for the precise prevention and treatment of aortic aneurysms through EV-based integrated diagnostic and therapeutic strategies.

Keywords:  abdominal aortic aneurysm; exosomes; extracellular vesicles; liquid biopsy; macrophage polarization; targeted therapy; thoracic aortic aneurysm; vascular smooth muscle cell

DOI:  https://doi.org/10.13345/j.cjb.260197
Crit Rev Oncol Hematol. 2026 Jul 26. pii: S1040-8428(26)00389-6. [Epub ahead of print]225 105502

Extracellular vesicle-mediated immunity-coagulation interaction in cancer-associated thrombosis during the immunotherapy era.

Jinghan Song, Jie Xu, Hui Xiao.

  Cancer-associated thrombosis represents one of the major causes of mortality in patients with malignancies. In the era of immunotherapy, particularly with the widespread use of immune checkpoint inhibitors, thromboembolic events have emerged as an increasingly recognized complication. Extracellular vesicles (EVs), as small extracellular vesicles that facilitate intercellular communication, are now understood to play a pivotal role at the intersection of immune activation and coagulation. They transport diverse bioactive cargos, including tissue factor (TF), PD-L1, and proinflammatory noncoding RNAs, which together reprogram endothelial cells, platelets, and neutrophils toward a prothrombotic phenotype. During immune checkpoint inhibitor therapy, cytokine-driven EV release is amplified, increasing the systemic burden of procoagulant vesicles while simultaneously modulating the therapeutic efficacy of immune checkpoint blockade. This EV-mediated immune-coagulative interaction defines a proposed "inflammation-EV-coagulation axis," offering a mechanistic rationale for the rising incidence of cancer-associated thrombosis in immunotherapy-treated patients. Beyond their pathogenic role, EVs also present translational opportunities. Circulating TF⁺/PD-L1⁺ EVs link immune efficacy with thrombotic risk and can be dynamically monitored through advanced assays. Combined exosomal signatures improve prediction of immune checkpoint inhibitor response and toxicity, while targeting EV secretion offers a novel "antithrombotic without immune suppression" therapeutic strategy. Future directions include AI-driven models integrating exosomal, coagulation, and imaging data to enable early identification of high-risk patients and accurate cancer-associated thrombosis prediction. These advances highlight EVs' role in linking immunity and coagulation during immunotherapy, which can lead to new diagnostic and therapeutic strategies for mitigating cancer-associated thrombosis in the immunotherapy era.

Keywords:  Cancer-associated thrombosis; Extracellular vesicles; Immunotherapy

DOI:  https://doi.org/10.1016/j.critrevonc.2026.105502
Blood Adv. 2026 Aug 11. 10(15): 5250-5252

Thrombin reprograms endothelial extracellular vesicles.

Paresh Kulkarni, Keith R McCrae.

DOI: https://doi.org/10.1182/bloodadvances.2026020305