bims-evecad 2026-06-28 papers

bims-evecad

Biomed News

on Extracellular vesicles and cardiovascular disease

Issue of 2026–06–28
eight papers selected by
Cliff Dominy

Stem cell-derived extracellular vesicles as immunomodulators: a novel paradigm for post-myocardial infarction repair and regeneration.
The Origin and Application of Cardiomyocyte-Derived Small Extracellular Vesicles: A Systematic Review.
Extracellular Vesicle-Derived MicroRNAs as Early Diagnostic Biomarkers of Diabetic Nephropathy and Cardiovascular Diseases in Type 2 Diabetes.
Large extracellular vesicles derived from red blood cells in coronary artery disease patients with anemia promote endothelial dysfunction.
m6A RNA Methylation-miRNA Crosstalk in Cardiovascular Remodeling.
Extracellular Vesicles Link Cerebral Ischemia to Coronary Microvascular Dysfunction - Role for RGD Motif-Activated Endothelin Signaling.
Alterations of Cerebral Extracellular Vesicle microRNA Profiling Potentially Disrupts Brain Homeostasis Following Myocardial Infarction.
Eosinophil-derived apoptotic extracellular vesicles accelerate steatotic liver repair after ischemia/reperfusion injury through mitochondria-associated metabolic reprogramming.

Front Pharmacol. 2026 ;17 1860228

Stem cell-derived extracellular vesicles as immunomodulators: a novel paradigm for post-myocardial infarction repair and regeneration.

Ali Raza, Panpan Wang, Fengjie Liu, Shumaila Arshad, Mulazim Hussain Asim, Zhenjiang Yang, Yu Cai.

  Myocardial infarction (MI) initiates a rapid and highly coordinated immune response that is essential for the clearance of necrotic tissue and activation of reparative processes. However, prolonged or dysregulated post-MI inflammation can exacerbate myocardial injury, promote adverse cardiac remodeling, and ultimately contribute to heart failure. Although current therapeutic strategies improve survival and symptom management, they remain limited in their ability to restore lost cardiomyocytes or effectively modulate the post-infarction immune microenvironment. In this context, stem cell-derived extracellular vesicles (EVs) have emerged as promising cell-free therapeutic candidates due to their immunomodulatory, regenerative, and paracrine properties. These nanoscale vesicles carry a diverse cargo of bioactive molecules, including microRNAs, proteins, lipids, and other signaling mediators that regulate intercellular communication and tissue repair. EVs derived from mesenchymal stem cells, cardiac progenitor cells, and induced pluripotent stem cells have demonstrated the ability to modulate key immune pathways by attenuating neutrophil-mediated inflammatory injury, promoting macrophage polarization towards a reparative M2 phenotype, and regulating T-cell responses by suppressing pro-inflammatory activity while enhancing regulatory T-cell function. Collectively, these effects help restore immune homeostasis and reduce adverse cardiac remodeling following MI. Moreover, advances in EVs engineering, cargo modification, and targeted delivery systems may enhance their therapeutic efficacy and translational potential. However, several critical challenges, including large-scale production, cargo heterogeneity, and the lack of standardized protocols for isolation and characterization, still need to be addressed before successful clinical translation. This review summarizes the current understanding of stem cell-derived EVs biology, comparative advantages over conventional and cell-based therapies, and their immunomodulatory mechanisms in post-MI repair. Moreover, it highlights recent innovations and the major challenges that must be addressed for successful clinical translation.

Keywords:  immunomodulators; macrophage polarization; myocardial infarction; regenerative medicine; stem cell-derived extracellular vesicles

DOI:  https://doi.org/10.3389/fphar.2026.1860228
Int J Med Sci. 2026 ;23(7): 2252-2276

The Origin and Application of Cardiomyocyte-Derived Small Extracellular Vesicles: A Systematic Review.

Shaojiao Liu, Yu Teng, Sha Su, Meng Wang, Lei Wang, Mingjing Zhao.

  Background/Aims: Cardiomyocyte-derived small extracellular vesicles (CM-sEVs) have emerged as important mediators of intercellular communication in cardiovascular diseases (CVDs). However, their origin-tracing markers, molecular signatures, and clinical applications remain incompletely characterized and lack systematic synthesis. This systematic review aimed to comprehensively evaluate CM-sEVs-specific markers, disease-associated cargos alterations, and their roles in intercellular communication.
Methods: A PRISMA-guided systematic search was conducted across major databases, including Web of Science, PubMed, Embase, and the Cochrane Library. Study screening, data extraction, and quality assessment were independently performed by two investigators according to predefined eligibility criteria.
Results: Thirty-four studies were included and three sets of information were systematically analyzed. Ldb3, Ambra1, and CD172a were verified as potential origin-tracing markers of CM-sEVs, and miR-208a, cTnT/Tnnt2, and α-MHC/Myh6 served as auxiliary markers. Several CM-sEVs-associated molecules, including CD172a, Ambra1, miR-9-5p, and lncRNA HCG15, demonstrated diagnostic or prognostic potential in CVDs populations. Functionally, CM-sEVs regulate fibrosis, angiogenesis, autophagy, and immune responses through cardiomyocyte-noncardiomyocyte communication networks.
Conclusion: This review systematically summarizes current evidence on potential origin-tracing markers, cargos characteristics, and intercellular communication roles of CM-sEVs, providing a theoretical basis for their identification and translational application in cardiovascular diseases.

Keywords:  biomarkers; cardiomyocytes; cardiovascular diseases; intercellular communication; small extracellular vesicles

DOI:  https://doi.org/10.7150/ijms.133199
Int J Mol Sci. 2026 Jun 20. pii: 5581. [Epub ahead of print]27(12):

Extracellular Vesicle-Derived MicroRNAs as Early Diagnostic Biomarkers of Diabetic Nephropathy and Cardiovascular Diseases in Type 2 Diabetes.

Yessenbekova Arailym, Arman Abaildayev, Belkozhayev Ayaz.

  Type 2 diabetes mellitus (T2DM) is a major driver of chronic kidney disease and cardiovascular morbidity worldwide. Extracellular vesicles (EVs), particularly exosomes, carry microRNAs (miRNAs) that reflect the pathophysiological state of their parent cells and represent promising non-invasive biomarkers. This review comprehensively examines the diagnostic and mechanistic roles of EV-derived miRNAs in diabetic nephropathy (DN) and cardiovascular diseases (CVDs) associated with T2DM. A PRISMA-guided literature search of PubMed, Scopus, Web of Science, and Embase identified 847 articles published between January 2020 and June 2026, of which 156 studies met the inclusion criteria. Several urinary exosomal miRNAs demonstrated significant diagnostic performance for DN, including miR-4534 (AUC = 0.786), miR-136-5p (sensitivity 72.2%, specificity 78.4%), and miR-142-3p. A meta-analysis of circulating miRNAs in diabetic kidney disease reported a pooled AUC of 0.79. In the cardiovascular setting, exosomal miR-155-5p (AUC = 0.901), miR-15a-3p (AUC = 0.874), and a four-miRNA panel (miR-433-3p/let-7b/miR-30-5p/miR-122-5p; AUC = 0.833) demonstrated strong diagnostic performance for ischemic heart disease and carotid atherosclerosis in T2DM. Mechanistically, key EV-associated miRNAs, including miR-21, miR-192, and the anti-fibrotic miR-29 family, participate in fibrosis, inflammation, oxidative stress, endothelial dysfunction, and cardiac remodeling pathways. EV-derived miRNAs therefore represent highly promising non-invasive biomarkers for the early diagnosis and monitoring of diabetic renal and cardiovascular complications. However, clinical translation requires standardized EV isolation and miRNA detection protocols, together with validation in large multicenter prospective cohorts. This review highlights the considerable diagnostic and translational potential of EV-derived miRNAs for precision medicine and liquid biopsy applications in T2DM complications.

Keywords:  atherosclerosis; biomarkers; clinical translation; exosomes; extracellular vesicles; liquid biopsy; miR-192; miR-21; microRNA; type 2 diabetes mellitus

DOI:  https://doi.org/10.3390/ijms27125581
J Mol Cell Cardiol. 2026 Jun 26. pii: S0022-2828(26)00095-7. [Epub ahead of print]

Large extracellular vesicles derived from red blood cells in coronary artery disease patients with anemia promote endothelial dysfunction.

Isabella Solga, Leon Götzmann, Vithya Yogathasan, Patricia Wischmann, Tin Yau Pang, Patricia Kleimann, Sebastian Temme, Lina Hofer, Anja Stefanski, Alexander Lang, Georg Nickenig, Christian Jung, Norbert Gerdes, Mohammed Rabiul Hosen, Malte Kelm, Ramesh Chennupati.

  Endothelial dysfunction (ED) is a hallmark of cardiovascular disease (CVD). We recently showed that anemia is associated with the progression of ED after acute myocardial infarction (AMI), which is partly mediated by red blood cells (RBCs). Extracellular vesicles (EVs) are efficient communicators between cells and can functionally contribute to various CVDs, including AMI. The potential role of RBC-derived large extracellular vesicles (REVs) in anemia-associated ED in stable coronary artery disease (CAD) patients has not yet been investigated. We hypothesize that REVs, but not plasma-derived EVs (PLEVs), mediate ED in anemic CAD patients. In this study, we demonstrated an increased release of REVs, but not PLEVs, in anemic patients compared to non-anemic patients. These REVs showed enhanced nitric oxide (NO) consumption in anemic patients. REVs and PLEVs were dose-dependently taken up by endothelial cells (ECs) in vitro. Aortic rings co-incubated with REVs, but not PLEVs, from anemic patients showed an attenuated endothelial NO-dependent (EDNO) relaxation. Mice injected with REVs from anemic patients showed impaired flow-mediated dilation responses in vivo, accompanied by reduced NO bioavailability. Proteomic analysis of REVs from anemic patients revealed increased myeloperoxidase (MPO) abundance. Co-incubation of ECs with REVs but not PLEVs from anemic patients increased reactive oxygen species (ROS) production. Pre-treatment of anemic REVs with an MPO inhibitor AZD-5904, followed by co-incubation with aortic rings, improved EDNO relaxation. These findings suggest that anemia increases the release of REVs with enhanced NO consumption. Additionally, anemic REVs promote ED in ECs by delivering oxidative stress-promoting MPO and increasing ROS production.

Keywords:  Anemia; Endothelial dysfunction; Extracellular vesicles; Myeloperoxidase; Nitric oxide; Red blood cells

DOI:  https://doi.org/10.1016/j.yjmcc.2026.06.010
Biomolecules. 2026 Jun 11. pii: 858. [Epub ahead of print]16(6):

m6A RNA Methylation-miRNA Crosstalk in Cardiovascular Remodeling.

Liujie Long, Yi Yang, Chufang Zheng, Kang Kang.

  Cardiovascular remodeling, encompassing vascular remodeling, myocardial remodeling, and fibrosis-associated tissue remodeling, underlies atherosclerosis, pulmonary hypertension, myocardial infarction, myocardial fibrosis, and other cardiovascular diseases. Its regulation has traditionally been studied through transcriptional, inflammatory, metabolic, mechanical, and intercellular signaling mechanisms. Recent advances in epitranscriptomics have identified N6-methyladenosine (m6A) RNA methylation as an additional post-transcriptional layer that interacts with microRNA (miRNA) pathways during cardiovascular disease progression. This review summarizes current evidence for m6A-miRNA crosstalk in cardiovascular remodeling, focusing on epitranscriptomic checkpoints that regulate miRNA fate, feedback-like regulatory circuits involving miRNAs and the m6A machinery, and cell-type-specific programs across endothelial cells, vascular smooth muscle cells, fibroblasts, and cardiomyocytes. We further discuss emerging analytical technologies and translational implications of this regulatory axis. Future studies should clarify causal mechanisms, cell-type and disease-stage specificity, and translational feasibility. Together, this multilayered framework provides a systems-level perspective on how RNA regulatory networks may shape pathological remodeling in cardiovascular disease.

Keywords:  cardiomyocytes; cardiovascular disease; endothelial cells; epitranscriptomics; extracellular vesicles; fibroblasts; m6A; non-coding RNAs; vascular remodeling; vascular smooth muscle cells

DOI:  https://doi.org/10.3390/biom16060858
J Cardiovasc Transl Res. 2026 Jun 25. pii: 77. [Epub ahead of print]19(1):

Extracellular Vesicles Link Cerebral Ischemia to Coronary Microvascular Dysfunction - Role for RGD Motif-Activated Endothelin Signaling.

Marta Balogh, Melina Tangos, Vijay S Patel, Nazha Hamdani, Zsolt Bagi.

  Ischemic stroke is associated with increased risk of subsequent cardiac ischemic events, yet mechanisms linking cerebral ischemia to coronary dysfunction remain unclear. We hypothesized that ischemic stroke directly impairs coronary microvascular function through circulating factors released after cerebral ischemia. We found that the vasodilator function of coronary arterioles (CA) was reduced in patients with prior ischemic stroke. In rats, transient middle cerebral artery occlusion impaired CA vasodilator function. Extracellular vesicles (EVs) isolated after cerebral ischemia and delivered into the rat CA lumen also impaired vasodilation. Moreover, we found that luminal delivery of RGD peptide attenuated flow-induced vasodilation in rat CA, an effect that was prevented by BQ-123, an endothelin ETA receptor antagonist. We propose that ischemic stroke directly induces coronary microvascular dysfunction via circulating EV-mediated, RGD-motif-dependent activation of endothelin signaling. This brain-heart vascular axis provides a mechanistic basis for increased post-stroke coronary risk and identifies EV-mediated pathways as potential therapeutic targets.

Keywords:  Arginine-Glycine-Aspartic Acid; Endothelin; Endothelium; Ischemic Stroke; Microparticle; Myocardial Ischemia; Vesicle

DOI:  https://doi.org/10.1007/s12265-026-10802-7
Biomolecules. 2026 May 26. pii: 776. [Epub ahead of print]16(6):

Alterations of Cerebral Extracellular Vesicle microRNA Profiling Potentially Disrupts Brain Homeostasis Following Myocardial Infarction.

Md Monowarul Islam, Shouyi Liang, Lijun Sun, Guoku Hu, Neha Dhyani, Lie Gao, Tara L Rudebush, Xue Xu, Jinpeng Liu, Irving H Zucker, Changhai Tian.

  Cognitive impairment (CI) is prevalent among heart failure (HF) patients. Although the brain injury in HF is multifactorial, oxidative stress and neuroinflammation are common pathological features of neurological disorders and are increasingly recognized as key mechanisms underlying CI. Extracellular vesicles (EVs) are well-established mediators of biological signaling in myocardial function and are widely recognized for transporting a variety of microRNAs. However, whether myocardial injury alters the miRNA profiles of brain EVs, potentially contributing to cognitive impairment (CI) by disrupting brain homeostasis, remains poorly understood. Using a rodent myocardial infarction (MI) model, we isolated brain EVs and characterized their miRNA profiling by means of small RNA sequencing. Our results demonstrate that miRNA profiles in brain EVs vary with HF progression. Only three miRNAs were significantly changed at 3 weeks post-MI, whereas thirty-two miRNAs and sixty-five miRNAs demonstrated significant changes post-MI, showed significant alterations at 6 and 12 weeks post-MI, respectively. Bioinformatic analysis suggests that some miRNAs against oxidative stress and inflammation were downregulated in brain EVs at 6 and 12 weeks post-MI. Conversely, several miRNAs responsible for oxidative stress and neuroinflammation were significantly increased, which may be of cardiac origin following MI. Collectively, these findings suggest that cardiac EVs may contribute to miRNA alterations in brain EVs, potentially driving CI by disrupting brain homeostasis.

Keywords:  cerebral extracellular vesicle; cognitive impairment; heart failure; neuroinflammation; oxidative stress

DOI:  https://doi.org/10.3390/biom16060776
J Nanobiotechnology. 2026 Jun 20.

Eosinophil-derived apoptotic extracellular vesicles accelerate steatotic liver repair after ischemia/reperfusion injury through mitochondria-associated metabolic reprogramming.

Chang Xiong, Liubing Chen, Zilong Rao, Jinyan Guo, Jiaming Ji, Zhenyu Yang, Jinyu Liu, Chengpeng Han, Ziqing Hei, Ying Bai, Weifeng Yao.

  Eosinophils have recently been recognized as hepatoprotective immune cells; however, cell-based therapies still face significant challenges. Apoptotic extracellular vesicles (ApoEVs) serve as critical cell-free alternatives capable of promoting tissue repair, yet exhibit marked functional heterogeneity dependent on their cell source. The therapeutic potential and mechanisms of eosinophil-derived ApoEVs (Eos-ApoEVs) in steatotic liver ischemia/reperfusion (I/R) injury remain elusive. Herein, treatment with Eos-ApoEVs effectively reversed oxygen-glucose deprivation/reperfusion (OGD/R)-induced cellular dysfunction in hepatocytes and liver sinusoidal endothelial cells (LSECs). Moreover, Eos-ApoEVs exerted potent immunomodulatory effects. Mechanistically, Eos-ApoEVs are enriched with functional mitochondria that fuse with damaged mitochondria in recipient cells, thereby reprogramming energy metabolism to promote hepatocyte proliferation, restore LSEC migration and tube-forming capacity, and facilitate anti-inflammatory macrophage polarization. To develop a clinically translatable therapeutic approach, we constructed a decellularized amniotic matrix (dAM)-based hydrogel patch (ApoEVs@dAM/HA-DA), which enables sustained release of ApoEVs and exhibits high biocompatibility. In a mouse model of steatotic liver I/R injury, transplantation of ApoEVs@dAM/HA-DA onto the liver surface significantly increased anti-inflammatory macrophage polarization, attenuated inflammation, promoted hepatocyte proliferation and enhanced angiogenesis, thereby accelerating liver repair. Thus, surface transplantation of ApoEVs@dAM/HA-DA provides a clinically viable and potent therapeutic strategy for steatotic liver I/R injury.

Keywords:  Amniotic membrane; Apoptotic extracellular vesicles; Eosinophils; Hydrogel; Ischemia-reperfusion injury; Mitochondrial; Steatotic liver

DOI:  https://doi.org/10.1186/s12951-026-04716-4