bims-evecad Biomed News
on Extracellular vesicles and cardiovascular disease
Issue of 2026–06–14
nine papers selected by
Cliff Dominy
  1. Exosome Therapy: A Novel Investigational Approach in Acute Myocardial Infarction.
  2. CD146 extracellular vesicles accumulate at atherosclerotic lesions, reducing inflammation and atheroma burden.
  3. Extracellular Vesicle-Based Strategies for the Prevention of Chemotherapy-Induced Cardiotoxicity.
  4. Extracellular vesicles MicroRNAs in stroke therapy: recent advances and translational potential.
  5. Macrophage PSRC1 attenuates atherosclerosis via extracellular vesicle-mediated MBD2 delivery to induce PCSK9 promoter methylation in hepatocytes.
  6. Pericardial fluid extracellular vesicles enhance angiogenesis and blunt cardiac fibrosis in coronary disease.
  7. Cardiac-targeted delivery of advanced medical therapies for heart disease.
  8. Targeted Delivery of mRNA to the Heart via Extracellular Vesicles or Lipid Nanoparticles.
  9. Proteomic Signatures of Adiposomes Track Cardiometabolic Risk Reduction Following Bariatric Surgery.
  1. Cardiol Rev. 2026 Jun 12.
    Exosome Therapy: A Novel Investigational Approach in Acute Myocardial Infarction.
    Aparna Joshi, Richa Gupta, Tsering Sangdup, Justin Jacob, Anjali Aggarwal.
      Despite major advances in reperfusion therapy and pharmacological management, acute myocardial infarction (AMI) remains one of the leading causes of mortality and morbidity worldwide. Conventional treatment strategies primarily focus on restoring coronary blood flow to ischemic myocardium; however, their ability to regenerate damaged cardiac tissue remains limited. In recent years, exosomes have emerged as a promising cell-free therapeutic approach for cardiac repair following AMI. Exosomes are nanosized extracellular vesicles secreted by various cell types that carry diverse bioactive molecules, including microRNAs, proteins, lipids, and signaling factors, which mediate intercellular communication and regulate multiple biological processes involved in myocardial healing. Emerging experimental and preclinical evidence suggests that exosome-based therapy may attenuate inflammation, reduce cardiomyocyte apoptosis, enhance angiogenesis, modulate immune responses, and promote myocardial regeneration following ischemic injury. Compared with conventional stem cell therapy, exosomes offer several advantages, including lower immunogenicity, reduced risk of tumorigenicity, improved stability, and easier storage and handling. Furthermore, engineered exosomes and targeted delivery systems are being investigated to enhance therapeutic specificity and efficacy in cardiovascular diseases. In addition to their therapeutic potential, circulating exosomes are also being explored as diagnostic and prognostic biomarkers for the early detection and monitoring of AMI. This review highlights the biological characteristics of exosomes, their mechanisms of action in myocardial repair, current experimental and clinical evidence, and future perspectives of exosome-based therapeutics in the management of AMI.
    Keywords:  acute myocardial infarction; exosomes; intranasal; mechanism; therapy
    DOI:  https://doi.org/10.1097/CRD.0000000000001365
  2. Atherosclerosis. 2026 May 29. pii: S0021-9150(26)00163-2. [Epub ahead of print]418 120797
    CD146 extracellular vesicles accumulate at atherosclerotic lesions, reducing inflammation and atheroma burden.
    Cléa Dubrou, Muriel G Blin, Karim Fallague, Richard Bachelier, Stéphanie Simoncini, Corinne Chareyre, Stéphane Robert, Alexandrine Bertaud, Romaric Lacroix, Françoise Dignat-George, Nathalie Bardin, Marcel Blot-Chabaud, Aurélie S Leroyer.
      Atherosclerosis remains the most important cause of death worldwide despite an extensive therapeutic arsenal. We previously showed that CD146, an adhesion molecule expressed by endothelial cells, is harbored by macrophages in atherosclerotic plaque and allows to reduce CCL5 and subsequent inflammation. As extracellular vesicles may serve as potential clinical delivery devices, we hypothesized that CD146 extracellular vesicles injection could be atheroprotective. We generated and purified extracellular vesicles from mouse endothelial cells deleted or not with CD146. In vitro stimulation of macrophages with CD146 extracellular vesicles induced macrophage polarization towards an anti-inflammatory phenotype through the STAT3/IL-10 axis, whereas CD146-negative extracellular vesicles did not have any effect. We next tracked the trafficking of labeled extracellular vesicles after intravenous injection in atherosclerotic ApoE-/- mice and visualized their incorporation into atheroma. After bi-weekly injections of extracellular vesicles for 6 weeks, only ApoE-/- mice treated with CD146 extracellular vesicles exhibited a significant reduction in atherosclerotic plaque, associated with an anti-inflammatory macrophage phenotype. We thus propose that treatment with CD146 extracellular vesicles could constitute a novel therapeutic option for reducing atherosclerosis.
    DOI:  https://doi.org/10.1016/j.atherosclerosis.2026.120797
  3. Ther Clin Risk Manag. 2026 ;22 597871
    Extracellular Vesicle-Based Strategies for the Prevention of Chemotherapy-Induced Cardiotoxicity.
    Zhaoqin Shen, Jie Qiu, Wei Yu, Rumeng Chen, Yuancong Jiang.
      Chemotherapy-induced cardiotoxicity (CIC) is a major limitation of modern anticancer therapy, particularly with anthracyclines and targeted agents, and contributes to long-term cardiovascular complications in cancer survivors. Extracellular vesicles (EVs) are nanoscale lipid-bilayer particles that mediate intercellular communication through the transfer of proteins, nucleic acids, and lipids. Emerging evidence indicates that EVs play a dual role in CIC. On one hand, EVs released from tumor cells or stressed cardiomyocytes can propagate cardiotoxic signals by modulating pathways related to oxidative stress, mitochondrial dysfunction, apoptosis, and inflammatory responses. On the other hand, EV-associated molecular cargo, including specific microRNAs and proteins, shows promise as minimally invasive biomarkers for early detection and monitoring of cardiac injury during chemotherapy. In addition, EVs derived from stem or progenitor cells, as well as engineered EVs with modified cargo or surface ligands, have demonstrated cardioprotective potential by attenuating oxidative damage, suppressing apoptosis, and modulating immune and inflammatory signaling in the injured myocardium. Despite these advances, several barriers hinder clinical translation, including vesicle heterogeneity, limited targeting specificity, challenges in standardized isolation and characterization, and insufficient safety and efficacy validation. This review summarizes the mechanistic roles of EVs in the development of CIC, highlights their emerging value as diagnostic biomarkers and therapeutic carriers, and discusses current technical challenges and future directions for translating EV-based strategies into clinical cardio-oncology practice.
    Keywords:  cancer; chemotherapy-induced cardiotoxicity; extracellular vesicles; precise prevention
    DOI:  https://doi.org/10.2147/TCRM.S597871
  4. Neuroscience. 2026 Jun 12. pii: S0306-4522(26)00383-0. [Epub ahead of print]
    Extracellular vesicles MicroRNAs in stroke therapy: recent advances and translational potential.
    Yanxin Ding, Yu Ma, Jie Hu, Mengzhen Wei, Hao Liao, Ying Yang, Jian Gu, Rui Tan.
      Ischemic stroke accounts for ∼ 87% of all strokes. Existing reperfusion therapies are limited by narrow time windows. Small extracellular vesicles (sEVs) can cross the blood-brain barrier and deliver microRNAs (miRNAs) that modulate post-stroke inflammation, apoptosis, angiogenesis, and neurogenesis. However, most evidence is from preclinical studies (MCAO models), and no approved clinical protocols exist. This review summarizes ischemic stroke pathogenesis and critically evaluates preclinical advances in sEV-miRNA therapy. We highlight key translational barriers: lack of standardized sEV isolation (MISEV2023), miRNA cargo heterogeneity, dosing uncertainties, limited biodistribution data, off-target risks, regulatory bottlenecks, and absence of stroke-specific trials. We also evaluate exosomal miRNAs from various cell sources (e.g., bone marrow mesenchymal stem cells). This review provides a critical synthesis of preclinical evidence to establish a foundation for future translational research in precision stroke therapy.
    Keywords:  BBB; Extracellular vesicles; MiRNAs; Stroke
    DOI:  https://doi.org/10.1016/j.neuroscience.2026.06.008
  5. Cell Biosci. 2026 Jun 09.
    Macrophage PSRC1 attenuates atherosclerosis via extracellular vesicle-mediated MBD2 delivery to induce PCSK9 promoter methylation in hepatocytes.
    Tongwei Wu, Hui Huang, Xiaoqian Zhang, Xinyi Feng, Weiming Luo, Lilong Lin, Dan Liu, Hangyu Pan, Shaopeng Wang, Jierong Zhang, Xianyi Zhang, Zhigang Guo, Mengzhuo Yin, Shiping Cao, Yanan Zhang.
       BACKGROUND: Atherosclerotic cardiovascular disease (ASCVD) is driven by dysregulated lipid metabolism and chronic inflammation. However, the mechanisms governing immune-liver crosstalk in this context remain poorly defined. Proline/serine-rich coiled-coil protein 1 (PSRC1) is a known regulator of cholesterol metabolism, but whether macrophage-derived PSRC1 influences hepatic functions via intercellular communication is unknown.
    METHODS: The relationship between macrophage PSRC1 and hepatic PCSK9 was examined in patients with coronary artery disease and murine models. We employed AAV6-mediated macrophage-specific targeting and whole-body Psrc1⁻/⁻ mice to evaluate cell-type-specific effects. Macrophage-hepatocyte communication was investigated using transwell systems and genetic blockade of EV secretion (sh-Rab27a). The selectivity of EV cargo loading was validated by protease protection assays and TSG101 interaction analysis. In vivo EV tracking (DiI-labeling) and ChIP-qPCR for DNMT recruitment were performed to elucidate the systemic and epigenetic mechanisms.
    RESULTS: Macrophage PSRC1 expression was significantly reduced in atherosclerotic conditions and inversely correlated with hepatic PCSK9 levels. Macrophage-specific PSRC1 depletion alone was sufficient to recapitulate the systemic hypercholesterolemia and accelerated atherosclerosis observed in whole-body knockout models. PSRC1 was found to interact with TSG101 to promote the selective loading of MBD2 into the EV lumen, a process confirmed by protease protection. These MBD2-enriched EVs were preferentially sequestered by the liver after systemic administration. Mechanistically, transferred MBD2 functioned as an epigenetic scaffold, recruiting DNA methyltransferases (DNMT1/3A) to the PCSK9 promoter to drive CpG hypermethylation and transcriptional repression. In vivo, administration of MBD2-enriched EVs significantly reduced hepatic PCSK9 protein, lowered plasma cholesterol, and enhanced plaque stability in ApoE⁻/⁻ mice.
    CONCLUSIONS: Our findings uncover a novel macrophage-liver epigenetic axis where macrophage PSRC1 controls systemic cholesterol homeostasis by regulating the EV-mediated delivery of MBD2. This "Reader-recruits-Writer" mechanism provides a refined understanding of immune-metabolic crosstalk and suggests that engineered EV-based MBD2 delivery represents a promising therapeutic strategy for ASCVD.
    Keywords:  Atherosclerosis; Extracellular vesicles; PSRC1
    DOI:  https://doi.org/10.1186/s13578-026-01598-9
  6. Biomed Pharmacother. 2026 Jun 08. pii: S0753-3322(26)00648-7. [Epub ahead of print]200 119612
    Pericardial fluid extracellular vesicles enhance angiogenesis and blunt cardiac fibrosis in coronary disease.
    Ali Fatehi Hassanabad, Anshul S Jadli, Megan B Meechem, Darrell D Belke, Cameron DA Mackay, Griffin F Wong, Shubham Banga, Mohsen Hassani, Daniel Young, Justin F Deniset, Amir Sanati-Nezhad, Antoine Dufour, Paul Wm Fedak, Vaibhav B Patel.
       BACKGROUND: To date, we have lacked an understanding of how coronary artery disease (CAD) affects the extracellular vesicle (EV) profile of human pericardial fluid (PF) and there is a paucity of data querying whether PF-derived EVs have functional benefits. This study characterizes PF-derived EVs and assesses their impact on angiogenesis in vitro and in vivo.
    METHODS: PF was collected from patients with and without CAD. PF-derived EVs of different sizes were isolated and characterized using microfluidic resistive pulse sensing. Human coronary artery endothelial cells (HCAECs) were exposed to EVs. Uptake of EVs by HCAECs and their impact on cell proliferation was evaluated. HCAECs were analyzed for their migratory and angiogenic properties. The in vivo effects of PF-derived EVs were assessed using murine ischemia models. To elucidate putative mechanisms, proteomic analysis was performed followed by in silico pathway analysis and functional validation.
    RESULTS: Small and medium-sized EVs (sEV and mEV, respectively) were isolated from PF. HCAECs exposed to sEVs isolated from CAD patients exhibited a significant increase in proliferations, wound closure, and tube formation. Injection of sEVs isolated from the PF of patients with CAD into pericardial cavity of MI mice reduced cardiac fibrosis and improved cardiac function. Differential protein expression implicated key pathways in angiogenesis, apoptosis mitigation, and fibrosis as protective effects of PF-sEVs.
    CONCLUSION: We identify that PF-derived EVs exert cardioprotective effects by promoting angiogenesis and reducing fibrosis. Future studies should evaluate whether our findings can be recapitulated in a large animal model and a pilot clinical trial.
    Keywords:  Coronary artery disease; Extracellular vesicles; Pericardial fluid; Therapeutic benefits
    DOI:  https://doi.org/10.1016/j.biopha.2026.119612
  7. Eur Heart J. 2026 Jun 12. pii: ehag432. [Epub ahead of print]
    Cardiac-targeted delivery of advanced medical therapies for heart disease.
    Xiao Liu, Yan Miao, Shengjie Lu, Derek J Hausenloy.
      Cardiovascular diseases (CVD) are the leading causes of death and disability worldwide with their global burden on the rise due to the ageing population and escalating prevalence of CVD risk factors, such as diabetes, obesity, hypertension, and hyperlipidaemia. As such, new treatments are urgently needed to improve health outcomes in patients with CVD. However, the efficacy of emerging medical and advanced therapies for CVD may be hampered by their inadequate delivery to the heart. Established delivery strategies such as intramyocardial injection and catheter-based intracoronary delivery technologies require an invasive intervention, thereby limiting their clinical application. Although cardiotropic adeno-associated virus vectors, which target therapeutics to the heart are less invasive they have their own challenges in terms of immunogenicity. This article provides a state-of-the-art review of the recent advances in cardiac-targeting delivery systems including local intracoronary catheter-based delivery, cardiotropic adeno-associated viruses, extracellular vesicles, microbubbles, and nanoparticle delivery platforms, which have emerged as promising approaches for targeting the delivery of medical and advanced therapies such as small molecules, biologics, nucleic acid therapeutics, and gene therapies to the heart to combat CVD. However, challenges concerning immunogenicity, off-target effects, and delivery efficiency must be overcome to realize their therapeutic potential as safe and effective therapies. By leveraging surface modifications, cardiac-homing peptides, membrane cloaking, and organ-targeting technologies, the emerging cardiac-targeting delivery systems promise more effective medical and advanced therapies for a wide range of CVD, including ischaemic heart disease, heart failure, and cardiac arrhythmias.
    Keywords:  Acute myocardial infarction; Adeno-associated virus; Cardiac-targeting; Extracellular vesicles; Heart failure; Nanoparticles
    DOI:  https://doi.org/10.1093/eurheartj/ehag432
  8. J Extracell Vesicles. 2026 Jun;15(6): e70324
    Targeted Delivery of mRNA to the Heart via Extracellular Vesicles or Lipid Nanoparticles.
    Muhammad Nawaz, Benyapa Tangruksa, Sepideh Heydarkhan-Hagvall, Franziska Kohl, Hernán González-King Garibotti, Yujia Jing, Zahra Payandeh, Azadeh Reyahi, Karin Jennbacken, John Wiseman, Leif Hultin, Lennart Lindfors, Jane Synnergren, Hadi Valadi.
      Efficient and specific delivery of mRNA to target tissues is critical for maximising therapeutic benefits while minimising off-target effects and systemic toxicity. Systemic administration of mRNA using lipid nanoparticles (LNPs) or extracellular vesicles (EVs) typically leads to predominant accumulation in the liver. We hypothesised that cardiac-specific EVs could promote enhanced relative cardiac enrichment of delivered mRNA compared with non-cardiac EVs or LNPs. In mice, intravenous administration of cardiac progenitor cell-derived EVs (CPC-EVs) achieved the greatest relative cardiac selectivity of modified mRNA encoding vascular endothelial growth factor A (VEGF-A) to the heart, with reduced liver accumulation relative to non-cardiac EVs and LNPs. Cytokine profiling across seven organs revealed that LNP delivery triggered a widespread pro-inflammatory response, whereas CPC-EVs elicited only a localised and limited cytokine activation, suggesting a more favourable safety profile. Furthermore, direct intramyocardial injection of CPC-EVs not only led to efficient mRNA uptake by cardiac tissue and robust VEGF-A protein expression, but also minimal transcriptomic perturbation in the cardiac tissue, as confirmed by RNA-seq. In contrast, LNPs and non-cardiac EVs induced widespread perturbation in the transcriptome of cardiac tissue. Functionally, VEGF-A mRNA delivery via CPC-EVs markedly increased CD31 and α-SMA expression and vessel formation in ex vivo aortic ring assays, confirming enhanced angiogenic potential. Together, these findings support CPC-EVs as a promising platform for achieving enhanced cardiac delivery of mRNA, with reduced liver accumulation, limited off-target transcriptomic perturbation, a more selective cytokine response, and enhanced angiogenic activity in ex vivo assays.
    Keywords:  VEGF‐A; extracellular vesicles; lipid nanoparticles; systemic administration; targeted mRNA delivery
    DOI:  https://doi.org/10.1002/jev2.70324
  9. Int J Mol Sci. 2026 May 29. pii: 4939. [Epub ahead of print]27(11):
    Proteomic Signatures of Adiposomes Track Cardiometabolic Risk Reduction Following Bariatric Surgery.
    Monica C Asada, Mohamed Saad Rakab, Imaduddin Mirza, Giorgia Scichilone, Mohammed H Morsy, Amro Mostafa, Francesco M Bianco, Mohamed M Ali, Chandra Hassan, Mario A Masrur, Abeer M Mahmoud.
      Adipose tissue-derived extracellular vesicles (adiposomes) carry a protein cargo that we previously showed differs between obese and lean individuals. In this study, we investigate how adiposomal protein cargo changes in response to sleeve gastrectomy and examine whether these changes are associated with clinical improvements. Twenty-three obese adults underwent pre- and post-bariatric surgery adipose sampling for adiposome isolation and clinical assessments that included vascular and metabolic profiles and inflammatory markers. The adiposomal protein cargo was analyzed via non-targeted proteomics. Differential protein abundance, pathway enrichment, and correlation analyses were assessed. Twelve weeks after bariatric surgery, BMI and fat mass decreased, accompanied by improved glucose and lipid profiles. Inflammatory markers (leptin, IL-6, CRP) also declined, while adiponectin and nitric oxide increased. Adiposomal proteomics identified 287 proteins, with 138 significantly altered. Downregulated proteins included PRDX2, FN1, SERPIND1, and inflammatory mediators; upregulated proteins included talin-1, fibrinogens, and adiponectin. Correlation analysis linked these changes to improvements in lipid profiles, vascular function, and circulating inflammatory markers. Pathway analysis revealed inhibition of lipid-regulatory pathways alongside enrichment of immune, metabolic, and vascular pathways, including lipoprotein metabolism and endothelial signaling. Bariatric surgery-induced cardiometabolic improvements were accompanied by adiposome proteomic remodeling, characterized by reduced inflammation and metabolic reprogramming.
    Keywords:  adiposomes; bariatric surgery; endothelial dysfunction; extracellular vesicles; inflammation; lipid metabolism; machine learning; obesity; proteomics; subcutaneous adipose tissue
    DOI:  https://doi.org/10.3390/ijms27114939
This page is being maintained by Thomas Krichel. It was last updated on 2026‒06‒15 at 16:21.