bims-evecad Biomed News
on Extracellular vesicles and cardiovascular disease
Issue of 2026–09–20
six papers selected by
Cliff Dominy
  1. Extracellular vesicles for abdominal aortic aneurysm: mechanisms, therapeutic potential, and translational challenges.
  2. Myocardial infarction treatment with a composite hydrogel containing metformin-induced vesicles of adipose-derived stem cells.
  3. Non-Coding RNAs from Cardiac Development to Disease: Regulatory Context, Regenerative Potential, and Translational Limits.
  4. Oscillatory shear stress-induced endothelial extracellular vesicles exacerbate aortic valve calcification.
  5. Investigation of plasma-derived extracellular vesicles in hypertrophic cardiomyopathy patients.
  6. Mitochondrial Distress Signals at the Heart-Liver Interface: Molecular Links Between MASLD and Heart Failure.
  1. Exp Biol Med (Maywood). 2026 ;251 11246
    Extracellular vesicles for abdominal aortic aneurysm: mechanisms, therapeutic potential, and translational challenges.
    Huibo Ma, Zongyou Xie, Yihang Cai, Fangda Li, Jianqiang Wu, Yuehong Zheng.
      Abdominal aortic aneurysm (AAA) is a progressive and potentially fatal vascular disease for which no effective pharmacological therapy is currently available. While surgical repair remains the only definitive treatment for advanced aneurysms, patients with small AAAs are mainly managed by surveillance, highlighting the need for disease-modifying strategies. Extracellular vesicles (EVs) have emerged as promising cell-free therapeutic tools because of their biocompatibility, ability to transfer bioactive cargo, and capacity to regulate multiple pathological processes involved in AAA progression. This review summarizes recent advances in EV-based therapies for AAA, focusing on mesenchymal stromal cell-derived EVs, immune cell-derived EVs, and engineered EV platforms. Preclinical studies suggest that therapeutic EVs can attenuate aneurysm formation by suppressing macrophage-driven inflammation, regulating macrophage polarization, inhibiting neutrophil extracellular trap-associated injury, protecting vascular smooth muscle cells from senescence, ferroptosis, apoptosis, and mitochondrial dysfunction, and limiting extracellular matrix degradation. Engineered EVs, including cargo-enriched, peptide-targeted, magnetically guided, chemotaxis-enabled, and biomaterial-assisted systems, may further improve lesion targeting, vascular retention, and therapeutic potency. However, EV-based AAA therapy remains at an early preclinical stage. Key barriers include unclear biodistribution and clearance, insufficient evidence of lesion-specific target engagement, heterogeneous EV isolation and characterization methods, uncertain dosing strategies, and the need for standardized potency, safety, manufacturing, and regulatory frameworks. Overall, EVs offer a biologically rational platform for non-surgical AAA therapy, but clinical translation requires rigorous standardization and robust evidence linking EV delivery to vascular repair.
    Keywords:  abdominal aortic aneurysm; cell-free therapy; engineered EVs; extracellular vesicles; precision medicine; translational challenges
    DOI:  https://doi.org/10.3389/ebm.2026.11246
  2. Mater Today Bio. 2026 Oct;40 103635
    Myocardial infarction treatment with a composite hydrogel containing metformin-induced vesicles of adipose-derived stem cells.
    Jing Qi, Zhipeng Cao, Lu Yin, Hong Jin, Cheng Cheng, Xiaohong Wang.
      Myocardial infarction (MI) leads to irreversible cardiomyocyte loss and adverse remodeling. Mesenchymal stem cell-derived extracellular vesicles (EVs) have shown promise in cardiac repair, but their clinical translation has been strictly limited by the short retention time and rapid clearance phenomena at the injury site. Metformin preconditioning of adipose-derived stem cells (ADSCs) is an effective way to enhance the yield of the EVs (Met-EVs). In this study, we incorporated Met-EVs into a composite hydrogel composed of decellularized extracellular matrices (dECMs) derived from porcine cardiac muscle and aortic adventitia, enabling sustained EV release and attenuation of inflammation after MI. In a rat MI model, the Met-EVs-laden dECM hydrogel (Met-EVs-dECM) significantly improved cardiac function recovery by enhancing cardiomyocyte survival, reducing cardiac apoptosis, and promoting angiogenesis. C1q/tumor necrosis factor-related protein 1 was identified as a contributor to the biological effects of Met-EVs, at least in part through the PI3K/AKT signaling pathway. Collectively, these findings demonstrate the therapeutic potential of the Met-EV-loaded dECM hydrogel for myocardial repair after MI.
    Keywords:  Apoptosis; C1q tumor necrosis factor-related protein 1; Decellularized extracellular matrix (dECM); Extracellular vesicles (EVs); Metformin; Myocardial infarction (MI)
    DOI:  https://doi.org/10.1016/j.mtbio.2026.103635
  3. Int J Mol Sci. 2026 Aug 31. pii: 7793. [Epub ahead of print]27(17):
    Non-Coding RNAs from Cardiac Development to Disease: Regulatory Context, Regenerative Potential, and Translational Limits.
    Le Wang, Yuyang Zhao, Ruiyang Zhang, Xuan Ning, Bo Jin.
      Non-coding RNAs (ncRNAs) are often reviewed as lists of molecules associated with individual cardiovascular phenotypes. Here, we instead ask how ncRNAs alter the probability, timing, and stability of cardiovascular cell-state transitions across development, injury, and disease. We organize evidence for microRNAs, long non-coding RNAs, circular RNAs, and extracellular-vesicle-associated RNAs around four regulatory operations: chromatin and transcriptional competence, post-transcriptional tuning, multicellular communication, and persistence or reversibility of the response. Cardiac development provides the reference trajectory from mesoderm specification through progenitor commitment, morphogenesis, and functional maturation. Regeneration is evaluated separately from DNA synthesis or cardioprotection and requires daughter-cardiomyocyte formation, maturation, electrical integration, scar replacement, and durable functional recovery. The disease section uses a bounded cardiovascular scope: atherosclerosis and hypertension are included as determinants of coronary supply and ventricular load, whereas renal and pulmonary examples are restricted to mechanisms that directly affect cardiac afterload or ventricular adaptation. Across these settings, the most recurrent ncRNAs are not universal switches; their effects depend on cell identity, subcellular localization, endogenous abundance, dose, and disease phase. We therefore grade mechanistic claims by target engagement, cell and species specificity, physiological stoichiometry, in vivo rescue, and human validation. This framework converts a molecule-by-molecule catalogue into a critical account of when ncRNAs are causal regulators, context-dependent modifiers, or biomarkers of changing tissue composition.
    Keywords:  RNA therapeutics; cardiac development; cardiac regeneration; cardiomyocyte proliferation; cardiovascular disease; circulating biomarkers; extracellular vesicles; non-coding RNA
    DOI:  https://doi.org/10.3390/ijms27177793
  4. Cardiovasc Res. 2026 Sep 16. pii: cvag205. [Epub ahead of print]
    Oscillatory shear stress-induced endothelial extracellular vesicles exacerbate aortic valve calcification.
    Shiqi Chen, Xiaoke Shang, Jianjun Xu, Zhengfeng Fan, Shaoshao Zhang, Rui Li, Ming Liu, Zhou Liu, Leilei Fan, Junwei Liu, Xin Jin, Tingwen Zhou.
       AIMS: Calcific aortic valve disease (CAVD) lacks effective pharmacotherapies. Although small extracellular vesicles (sEVs) are established mediators of cellular communication, how they translate oscillatory shear stress (OSS) into pro-calcific signals through endothelial-interstitial crosstalk remains unknown. This study aimed to delineate a complete mechanosensitive pathway by which sEVs drive aortic valve calcification (AVC).
    METHODS AND RESULTS: Using circRNA microarray sequencing, we identified circILRUN as the most markedly upregulated circRNA in sEVs from OSS-stimulated human valvular endothelial cells (hVECs). Endothelial-derived sEVs delivered circILRUN to human valvular interstitial cells (hVICs) and promoted osteogenic reprogramming of hVICs. Genetic ablation of circILRUN attenuated AVC in two independent mouse models, improving echocardiographic parameters and reducing calcium deposition. Mechanistically, circILRUN acted as a protein scaffold that recruited USP11 to NAT10, thereby stabilizing NAT10 via suppression of K48-linked ubiquitination. Integrated N4-acetylcytidine (ac4C) acetylome and transcriptome analyses identified CD36 as a key downstream target, with NAT10 catalyzing ac4C modification within its coding sequence to enhance CD36 mRNA stability and translation. Therapeutically, pharmacological inhibition of NAT10 reversed the pro-calcific effects of circILRUN in vitro and ameliorated AVC in vivo.
    CONCLUSIONS: Our study delineates a novel OSS induced sEV-circILRUN-NAT10-CD36 axis that integrates mechanical stress, epitranscriptomic regulation to drive AVC. These findings not only elucidate a fundamental mechanotransduction pathway in CAVD but also identify NAT10 as a candidate therapeutic target for clinical intervention.
    Keywords:  Calcific aortic valve disease; N4-acetylcytidine; circILRUN; small extracellular vesicles; valvular endothelial-interstitial cell crosstalk
    DOI:  https://doi.org/10.1093/cvr/cvag205
  5. iScience. 2026 Sep 18. 29(9): 117301
    Investigation of plasma-derived extracellular vesicles in hypertrophic cardiomyopathy patients.
    Alessandra Stefania Rizzuto, Andrea Faggiano, Chiara Macchi, Isabella Fichtner, Daniele Bianchi, Alice Mallia, Eleonora Gnan, Francesco Tafuri, Andrea Pandolfi, Michele Baroni, Stefania Paganini, Roberto Meazza, Ilaria Giusti, Vincenza Dolo, Paola Castronovo, Palma Finelli, Alberto Corsini, Marco Vicenzi, Roberto Sassi, Cristina Banfi, Massimo Walter Rivolta, Margherita Calcagnino, Stefano Carugo, Massimiliano Ruscica.
      Hypertrophic cardiomyopathy (HCM) is a genetically determined heart disease characterized by marked clinical heterogeneity and limited availability of specific circulating biomarkers that reflect underlying disease mechanisms. This study investigated whether plasma-derived extracellular vesicles (EVs) capture disease-related molecular features in patients with HCM. Plasma EVs were characterized for size, cellular origin, and protein cargo using flow cytometry and targeted and untargeted proteomic analyses. While size and concentration of EVs were comparable between groups, patients with HCM exhibited an enrichment of platelet-derived EVs (CD41a+) and reductions in neutrophil (CD66b+)- and lymphatic-endothelial-cell (CD310+)-derived EVs. Proteomic profiling revealed EV-associated proteins linked to platelet activation and thrombo-inflammation. Multivariable protein signatures derived from EVs discriminated patients from controls with performance comparable to plasma-based models and were not influenced by age. These findings indicate that plasma-derived EVs capture key biological pathways involved in HCM and may complement biomarker discovery strategies.
    Keywords:  biomarkers; cardiomyopathies; extracellular vesicles; heart diseases
    DOI:  https://doi.org/10.1016/j.isci.2026.117301
  6. Int J Mol Sci. 2026 Aug 28. pii: 7734. [Epub ahead of print]27(17):
    Mitochondrial Distress Signals at the Heart-Liver Interface: Molecular Links Between MASLD and Heart Failure.
    Xing Yang, Kun Cheng, Chen Chen, Yuxin Zhang, Dao Wen Wang.
      Metabolic dysfunction-associated steatotic liver disease (MASLD) and heart failure (HF) frequently coexist within a shared cardiometabolic environment, yet their mitochondrial abnormalities are stage- and phenotype-dependent rather than uniform. In MASLD, mitochondrial adaptation evolves from increased oxidative metabolism in early steatosis toward impaired respiratory flexibility, oxidative stress, and defective quality control with disease progression, whereas the failing myocardium develops reduced energetic reserve and altered substrate utilization. These organ-specific disturbances can modify mitochondria-linked metabolites, mitochondrial damage-associated molecular patterns, stress-responsive endocrine mediators, and extracellular vesicle-associated mitochondrial cargo. However, similar mitochondrial abnormalities or circulating signals in the liver and heart do not by themselves establish direct inter-organ communication. This review distinguishes shared systemic drivers and organ-intrinsic mitochondrial stress from source-resolved cardio-hepatic signaling, highlighting hepatic ketogenesis, fibroblast growth factor 21 (FGF21), mitochondrial DNA (mtDNA)-dependent inflammatory pathways, and extracellular vesicle-mediated cargo transfer as mechanistically distinct examples with different levels of evidence. We further discuss biomarker limitations, HF-related hemodynamic liver injury, and therapeutic strategies ranging from established cardiometabolic unloading to emerging mitochondria-centered interventions. A stage-, phenotype-, and source-resolved framework may improve interpretation of mitochondrial signals and guide future mechanistic and translational studies in the MASLD-HF overlap.
    Keywords:  cardio-hepatic crosstalk; heart failure; metabolic dysfunction-associated steatotic liver disease; mitochondrial distress signaling; mitochondrial dysfunction
    DOI:  https://doi.org/10.3390/ijms27177734
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