bims-evecad 2026-03-15 papers

bims-evecad

Biomed News

on Extracellular vesicles and cardiovascular disease

Issue of 2026–03–15
ten papers selected by
Cliff Dominy

Extracellular vesicles in cardiovascular disease: Biomarkers, therapeutic applications, and drug delivery strategies.
EV-Encapsulated Mitochondrial miRNAs: Enhancing Cardiomyocyte Bioenergetics.
Extracellular vesicles related to familial hypercholesterolemia.
TMAO-Triggered Endothelial-Mesenchymal Transition and Microvesicle Release as Mediators of Vascular Smooth Muscle Cell Osteogenic Differentiation and Vascular Calcification.
Exosome-delivered bioactive molecules regulate macrophage polarization in atherosclerosis and myocardial infarction: mechanisms and therapeutic potential.
Lachnospiraceae-Derived Extracellular Vesicles Mediate the Cardioprotective Effects of Barley Leaf in Myocardial Infarction by Improving Intestinal Stem Cell Function.
The Dual Role of Extracellular Vesicles in Aging and Age-Related Diseases: Pathophysiology and Therapeutic Potential.
Young Regulatory T Cell-Derived Extracellular Vesicles Improve Mitochondrial Function and Angiogenesis and Suppress Inflammation in Senescent Brain and Heart.
Mesenchymal Stem Cell-Derived Extracellular Vesicles in Myocardial Ischemia-Reperfusion Injury: A Comprehensive Review.
CircEif3c/miR-96-5p/PHF20L1/MEOX2 axis in perivascular preadipocyte exosomes mediates fibroblast dysfunction and vascular remodeling.

Clin Chim Acta. 2026 Mar 11. pii: S0009-8981(26)00154-3. [Epub ahead of print] 120972

Extracellular vesicles in cardiovascular disease: Biomarkers, therapeutic applications, and drug delivery strategies.

Qamar Abuhassan, Amirali Salajegheh, Faris Anad Muhammad, Ali Fawzi Al-Hussainy, Tushar B Gajjar, Malathi Hanumanthayya, Sandeep Kumar Shukla, Rajashree Panigrahi, Neeraj Bainsal, Djamila Polatova, Hayder Naji Sameer, Rasim M Salih, Mohaned Adil.

  Extracellular vesicles (EVs) have emerged as pivotal mediators of intercellular communication in cardiovascular disease (CVD), influencing inflammation, thrombosis, fibrosis, angiogenesis, and cardiac remodeling through the transfer of proteins, lipids, and RNAs. The presence of EVs in virtually all biofluids and their cargo's close linkage to cellular activation or injury make EVs attractive noninvasive biomarkers for CVD diagnosis, prognosis, and therapy monitoring, with circulating EV signatures reported in myocardial infarction, heart failure, atherosclerosis, and valvular and cardiomyopathic disorders. Parallel advances highlight EVs as cell-free therapeutic agents, recapitulating key paracrine benefits of stem and progenitor cell therapies while avoiding issues of low engraftment and arrhythmogenic risk. In addition to their endogenous activity, both native and engineered EVs are being actively developed as drug delivery platforms, offering biocompatibility, immune stealth, and the capacity to cross biological barriers, with promising data for targeted delivery to the ischemic myocardium and atherosclerotic plaques. Engineering strategies, including surface functionalization, controlled cargo loading, and combination with biomaterials such as hydrogels, can increase cardiac homing, prolong circulation, and improve on-target efficacy. Despite this promise, major hurdles remain: heterogeneity of EV subtypes, lack of standardized isolation and characterization workflows, low production yields, incomplete pharmacokinetic understanding, and unresolved regulatory classification. Addressing these limitations through multi-omics, advanced bioengineering, scalable bioprocessing, and rigorously designed clinical trials will be critical to integrate EV-based biomarkers, therapeutics, and delivery systems into cardiovascular precision medicine.

Keywords:  Biomarkers; Cardiovascular disease; Cell-free therapy; Drug delivery; Extracellular vesicles

DOI:  https://doi.org/10.1016/j.cca.2026.120972
Int J Mol Sci. 2026 Feb 26. pii: 2224. [Epub ahead of print]27(5):

EV-Encapsulated Mitochondrial miRNAs: Enhancing Cardiomyocyte Bioenergetics.

Dhienda C Shahannaz, Tadahisa Sugiura.

  Mitochondrial dysfunction lies at the core of numerous cardiac pathologies, yet restoring mitochondrial health remains a therapeutic frontier. In recent years, extracellular vesicles (EVs) have emerged as nature's delivery nanocarriers, capable of transporting a wide array of biomolecules, including mitochondrial-associated microRNAs (mito-miRs). These miRNAs regulate bioenergetics, redox homeostasis, and apoptotic signaling-making them prime candidates for non-cellular mitochondrial therapy. This review explores the evolving landscape of mitochondrial miRNA encapsulation within EVs, focusing on their potential to restore mitochondrial transcriptional and metabolic programs governing ATP synthesis and redox balance, enhance cellular energy output, and mitigate oxidative stress. We integrate insights from stem cell biology, RNA epigenetics, systems cardiology, and bioengineering, offering a unifying framework for therapeutic applications across ischemic heart disease, heart failure, and chemotherapy-induced cardiomyopathy. An integrative narrative synthesis of recent peer-reviewed literature was performed across major biomedical databases, prioritizing mechanistic studies linking EV-mediated mito-miR delivery to cardiomyocyte mitochondrial function. By harmonizing multi-omic signaling, vesicle engineering, and mitochondrial medicine, this review seeks to guide future research toward targeted, customizable, and scalable bioenergetic interventions-unlocking a next-generation path for cardiovascular regeneration.

Keywords:  RNA therapeutics; cardiomyocyte bioenergetics; extracellular vesicles (EVs); heart failure; miRNA engineering; mitochondrial microRNAs; non-cellular mitochondrial therapy; regenerative cardiology; systems biology; translational nanomedicine

DOI:  https://doi.org/10.3390/ijms27052224
Arch Endocrinol Metab. 2026 Apr 01. 70(2):

Extracellular vesicles related to familial hypercholesterolemia.

Júnea P de P Silvino, Cinthia E Jannes, Rodrigo M C Pestana, Lucas P de P Silvino, Iêda de F O Silva, Andréa Teixeira-Carvalho, Karina B Gomes.

   OBJECTIVE: This study aimed to evaluate extracellular vesicles (EVs) in a group of carriers of familial hypercholesterolemia (FH)-related genetic variants compared to those in family members without FH.
SUBJECTS AND METHODS: Annexin V-positive EVs (PS+-EVs), cardiomyocyte-derived EVs (CardioEVs), endothelial cell-derived EVs (EEVs), platelet-derived EVs (PEVs) and tissue factor-expressing EVs (TFEVs) were evaluated to compare individuals with FH and genetic variants (n = 16) and non-FH patients without genetic variants (n = 16).
RESULTS: Increased numbers of PS+-EVs, CardioEVs, EEVs and TFEVs were observed in the group c arrying genetic variants. Furthermore, patients with FH who did not use statins had higher counts of these same EVs than non-FH patients who did not use statins. These EVs were significantly correlated with low-density lipoprotein cholesterol (LDL-c) levels.
CONCLUSION: The data suggest that EVs are related to FH and that their cellular origins could be related to cardiovascular complications commonly observed in this disease.

Keywords:  Familial hypercholesterolemia; cardiovascular disease; extracellular vesicles; genetic variants

DOI:  https://doi.org/10.20945/2359-4292-2026-0022
Cells. 2026 Mar 05. pii: 466. [Epub ahead of print]15(5):

TMAO-Triggered Endothelial-Mesenchymal Transition and Microvesicle Release as Mediators of Vascular Smooth Muscle Cell Osteogenic Differentiation and Vascular Calcification.

Joumana Al Akhdar, Melike Nur Yangın Yılmaz, Kemal Baysal.

  Background: Cardiovascular diseases (CVDs) are the leading global cause of mortality, with vascular calcification (VC) as a major predictor of adverse outcomes. Although vascular smooth muscle cells (VSMCs) are established contributors, the role of endothelial cells (ECs), particularly via the endothelial-mesenchymal transition (EndMT) and exosome signaling, remains less defined. Objective: This study investigated whether the gut microbiota-derived metabolite Trimethylamine-N-oxide (TMAO) induces EndMT in ECs and whether exosomes from TMAO-treated ECs regulate the VSMC phenotype and calcification. Methods: Human umbilical vein endothelial cells (HUVECs) were exposed to TMAO at physiological and pathological levels (10-50 µM). EndMT markers were analyzed by Western blotting and qPCR. Exosomes were isolated, characterized, and applied to HAVSMCs in graded doses. Osteogenic and contractile markers, β-catenin signaling, and calcification were quantified. Exosomal miR-30 and miR-222 were studied. Results: TMAO triggered dose-dependent EndMT, decreasing CD31/VE-cadherin and increasing α-SMA, N-cadherin, and vimentin. Exosomes from TMAO-treated ECs reprogrammed VSMCs, downregulating contractile proteins and upregulating RUNX2, OPN, TNAP, and β-catenin, causing calcium accumulation. These exosomes displayed elevated miR-222 and reduced miR-30, changes that activated β-catenin signaling and promoted the osteogenic reprogramming of VSMCs. Conclusions: Pathophysiological TMAO levels induce EndMT and mediate the formation of exosomes, which drive the osteogenic reprogramming and calcification of VSMCs.

Keywords:  Trimethylamine-N-oxide; endothelial–mesenchymal transition; exosomes; miR-222; miR-30; non-coding RNA; osteogenic differentiation; vascular calcification; vascular smooth muscle cells; β-catenin

DOI:  https://doi.org/10.3390/cells15050466
Front Cardiovasc Med. 2026 ;13 1739907

Exosome-delivered bioactive molecules regulate macrophage polarization in atherosclerosis and myocardial infarction: mechanisms and therapeutic potential.

Yuanlin Zhou, Guanghe Ran, Hua Guo.

  Exosomes, by carrying biologically active molecules, constitute the core network of inter-cell communication and play an important role in the regulation of macrophage polarization. The dynamic balance of macrophage polarization is a key determinant of atherosclerosis plaque stability and cardiac repair after myocardial infarction. This review systematically summarizes the molecular mechanisms by which exosomes and their specific molecules accurately regulate M1/M2 polarization of macrophages. We also focused on the mechanism of action by which exosomes play a dual role in promoting or inhibiting the physiological and pathological environment of AS and MI. In addition, the clinical transformation potential and current challenges of new biomarkers and treatment strategies (such as engineered exosomes, drug carriers) are also discussed, which is expected to bring new treatment strategies to the treatment of cardiovascular diseases.

Keywords:  atherosclerosis; exosome; macrophage; myocardial infarction; polarization

DOI:  https://doi.org/10.3389/fcvm.2026.1739907
J Extracell Vesicles. 2026 Mar;15(3): e70250

Lachnospiraceae-Derived Extracellular Vesicles Mediate the Cardioprotective Effects of Barley Leaf in Myocardial Infarction by Improving Intestinal Stem Cell Function.

Wenjing Chen, Yifan Zhao, Qian Zhao, Yingzhuo Zhou, Chen Ma, Li Dong, Yinghua Luo, Zhong Zhang, Fang Chen, Xiaosong Hu, Daotong Li.

  Ischaemic cardiovascular diseases, particularly myocardial infarction (MI), remain the leading causes of morbidity and mortality worldwide. Targeting extracellular vesicles (EVs) from the gut microbiota by diet may provide opportunities to improve cardiovascular health. Barley leaf (BL) has a long history of use in Traditional Chinese medicine and has been found to beneficially influence the gut microbial composition. Herein, we used a murine model of MI to explore the mechanistic role of gut bacteria-derived EVs in the cardioprotective effects of BL. Dietary supplementation of BL remarkably improved cardiac function and ameliorated adverse remodelling in experimental MI. The cardioprotective effects of BL were linked to enhanced gut epithelial barrier and suppressed transfer of bacterial-derived lipopolysaccharide. Moreover, BL alleviated MI-induced gut microbial dysbiosis, with an enrichment of Lachnospiraceae. Gut microbiota depletion by antibiotic treatment abolished the cardioprotective effects of BL. Furthermore, mice receiving microbiota from BL-fed mice had better cardiac outcomes after MI compared to mice receiving microbiota from mice without BL supplementation. Notably, we identified that BL increased the abundance of Lachnospiraceae_NK4A136_group, a commensal member of the family Lachnospiraceae. Supplementing antibiotic-treated mice with live but not heat-inactivated Lachnospiraceae ameliorated myocardial injury and cardiac remodelling in MI mice. We isolated EVs from Lachnospiraceae and demonstrated that Lachnospiraceae-derived EVs (L-EVs) achieved desirable biosafety, stability and colonic retention effects following oral administration. Mechanistically, estrogen-like metabolites from L-EVs modulated the estrogen receptor alpha (ERα)-solute carrier family 6 member 14 (Slc6a14)-Hippo signalling pathway to promote intestinal stem cell function and ultimately protected against MI-induced adverse remodelling. Our study thus provides novel insights into the role of the microbiota-gut-heart axis in the pathophysiology of MI and underscores the great potential of gut bacteria-derived EVs to reduce pathological outcomes after MI through improving gut health.

Keywords:  Lachnospiraceae; barley leaf; cardiac remodelling; extracellular vesicles; gut microbiota; myocardial infarction

DOI:  https://doi.org/10.1002/jev2.70250
Int J Nanomedicine. 2026 ;21 589123

The Dual Role of Extracellular Vesicles in Aging and Age-Related Diseases: Pathophysiology and Therapeutic Potential.

Yifan Zhu, Xiansong Fang, Shuli Zhang, Yiqun Liao, Haihong Lin, Puwen Chen, Mei Yang, Junyun Huang, Xiaoling Wang.

  Aging is a complex biological process characterized by progressive loss of physiological integrityand represents the primary risk factor for numerous chronic disorders, including neurodegenerative diseases, diabetes mellitus, cardiovascular disease, and stroke. Increasing evidence indicates that chronic low-grade inflammation ("inflammaging"), genomic instability, mitochondrial dysfunction, deregulated nutrient sensing, cellular senescence, and impaired intercellular communication collectively drive aging and age-related pathologies. Extracellular vesicles (EVs), a heterogeneous population of lipid bilayer-enclosed nanoparticles released by nearly all cell types, have emerged as critical regulators of these processes by mediating intercellular transfer of proteins, lipids, metabolites, and nucleic acids. In this review, we systematically synthesize current advances in EV biology within the context of aging and major age-related diseases, emphasizing their double-edged roles in disease pathogenesis and therapy. We discuss how senescent or diseased cell-derived EVs propagate inflammation, oxidative stress, genomic damage, mitochondrial dysfunction, and maladaptive immune responses, thereby accelerating tissue degeneration. Conversely, EVs derived from stem cells or young, healthy tissues exert therapeutic and rejuvenating effects by restoring redox balance, modulating immune polarization, enhancing mitochondrial function, regulating nutrient-sensing pathways, and promoting tissue repair and regeneration. Finally, we highlight the therapeutic potential of native and engineered EVs as diagnostic biomarkers and treatment modalities for aging and age-related diseases, while discussing key limitations, including rapid systemic clearance and targeting efficiency. Collectively, this review provides a comprehensive and therapy-oriented framework for understanding EVs as both drivers of aging-associated pathology and promising tools for anti-aging and regenerative medicine.

Keywords:  aging; cardiovascular disease; diabetes; extracellular vesicles; neurodegenerative diseases; stroke

DOI:  https://doi.org/10.2147/IJN.S589123
J Neurochem. 2026 Mar;170(3): e70402

Young Regulatory T Cell-Derived Extracellular Vesicles Improve Mitochondrial Function and Angiogenesis and Suppress Inflammation in Senescent Brain and Heart.

Jiahui Cheng, Yiyang Xia, Zhiqiang Ji, Lingling Xu, Rifeng Gao, Zhi Xiong, Lili Huang, Xiao Zhang, Weina Ding, Yawen Sun, Shiteng Suo, Bo Li, Yan Zhou.

  The core mechanisms underlying aging involve genomic instability, cellular senescence, mitochondrial dysfunction, and chronic inflammation, necessitating multi-dimensional therapeutic interventions. Treg-derived extracellular vesicles (Treg-EVs) therapy, which circumvents the safety risks associated with live cell therapies, exhibits the potential to modulate metabolic and immune functions, offering promise for healthy aging. Here, we isolated Tregs from young male C57BL/6 mice and collected Treg-EVs. In vitro experiments demonstrated that Treg-EVs significantly attenuated cellular senescence, reduced reactive oxygen species (ROS) accumulation, and enhanced mitochondrial respiration in HL-1 and HT22 senescent cell models. In vivo experimental data revealed that young Treg-EVs promoted mitochondrial biogenesis, facilitated vascular repair and regeneration, as well as attenuated inflammatory responses, and ultimately prolonged the survival of aged male C57BL/6 mice. This study demonstrates the ability of Treg-EVs therapy to reverse multiple aging-related abnormal phenotypes, providing a promising strategy for treating aging and its associated diseases.

Keywords:  Treg‐derived extracellular vesicles; aging; angiogenesis; inflammation; mitochondrial biogenesis

DOI:  https://doi.org/10.1111/jnc.70402
Biology (Basel). 2026 Feb 26. pii: 383. [Epub ahead of print]15(5):

Mesenchymal Stem Cell-Derived Extracellular Vesicles in Myocardial Ischemia-Reperfusion Injury: A Comprehensive Review.

Luca Bonanni, Nicola Ferri.

  Myocardial ischemia-reperfusion injury remains a major unresolved challenge in cardiovascular medicine. Although timely restoration of blood flow is essential to limit ischemic damage, reperfusion triggers a complex network of maladaptive biological responses, including oxidative stress, calcium overload, mitochondrial dysfunction, metabolic impairment, and sterile inflammation. These processes converge on cardiomyocyte death, adverse ventricular remodeling, and long-term functional deterioration. Mesenchymal stem cells have been widely investigated as cardioprotective agents; however, accumulating evidence indicates that their beneficial effects are predominantly mediated by paracrine mechanisms. Among these, extracellular vesicles released by mesenchymal stem cells have emerged as key biological effectors. Experimental studies demonstrate that mesenchymal stem cell-derived extracellular vesicles modulate multiple signaling pathways involved in ischemia-reperfusion injury, including activation of the phosphoinositide 3-kinase (PI3K) and protein kinase B (PKB) axis, regulation of signal transducer and activator of transcription 3 (STAT3) signaling in a cell-specific manner, suppression of nuclear factor kappa B (NF-κB)-driven inflammatory responses, and stabilization of hypoxia-inducible factor-1α (HIF-1α)-dependent adaptive programs. At the subcellular level, these vesicles preserve mitochondrial structure and function, support energy metabolism, regulate mitophagy, and limit oxidative damage. Their molecular cargo, comprising regulatory microRNAs, metabolic enzymes, and stress-response proteins, enables coordinated modulation of survival, inflammatory, and reparative pathways rather than single-target effects. This review synthesizes current experimental evidence on the mechanistic basis of mesenchymal stem cell-derived extracellular vesicle-mediated cardioprotection and discusses their potential as cell-free, mechanism-based therapeutic strategies to limit myocardial ischemia-reperfusion injury.

Keywords:  cardioprotection; extracellular vesicles; inflammation; ischemia–reperfusion injury; mesenchymal stem cells; mitochondrial dysfunction; myocardial infarction; signaling pathways

DOI:  https://doi.org/10.3390/biology15050383
Noncoding RNA Res. 2026 Aug;19 1-17

CircEif3c/miR-96-5p/PHF20L1/MEOX2 axis in perivascular preadipocyte exosomes mediates fibroblast dysfunction and vascular remodeling.

Yixuan Liu, Peiqing Tian, Shuaiyong Zhang, Jiayu Wang, Ye Zhang, Shuxin Ge, Qinghai Wang, Peng Wang, Juan Zhang, Ping Liu.

   Background: Diabetes mellitus is a major modifiable risk factor for atherosclerotic cardiovascular disease and pathological vascular remodeling. During chronic hyperglycemia, exosomes serve as essential nanocarriers that coordinate intercellular communication and induce structural and functional alterations in the vascular wall. Perivascular pre-adipocytes (PVPACs) exhibit high exosome secretory activity, while adventitial fibroblasts (AFs) are key effector cells in vascular remodeling. Despite their anatomical proximity, the potential bidirectional crosstalk between PVPAC-derived exosomes and AFs, and its roles for vascular remodeling, remains largely unexplored.
Methods: A co-culture system of PVPACs and AFs, along with a mouse model of perivascular proliferation, was established under sustained hyperglycemic conditions. Exosomes were isolated via sequential ultracentrifugation and characterized based on morphology, size distribution, and exosomal markers. High-throughput RNA microarray was employed to profile PVPAC-derived exosomal RNAs, with qRT-PCR and in situ hybridization used to validate the expression of circEif3c, miR-96-5p, PHF20L1, and MEOX2. Mechanistic studies integrated bioinformatic predictions, CRISPR-Cas9 editing, with bio-functional assays, including RNA pull-down, RIP, dual-luciferase reporter, CO-IP, and protein interaction analyses, to elucidate the circEif3c/miR-96-5p/PHF20L1/MEOX2 axis. In vitro and in vivo rescue experiments evaluated the role of exosomal circEif3c in AF proliferation, migration, apoptosis, and vascular remodeling.
Results: PVPAC-derived exosomes were enriched with circEif3c, which acted as a competitive endogenous RNA by sequestering miR-96-5p, thus alleviating its suppression of PHF20L1 and inhibiting MEOX2 signaling. This axis enhanced AF proliferation and migration, reduced apoptosis, and exacerbated vascular remodeling. Conversely, inhibition of exosomal circEif3c or overexpression of MEOX2 attenuated AF activation, promoted apoptosis, and markedly improved vascular remodeling in diabetic mice.
Conclusion: Our findings establish the PVPAC-derived exosomal circEif3c/miR-96-5p/PHF20L1/MEOX2 axis as a critical driver of hyperglycemia-induced vascular remodeling. Targeting this pathway presents a promising therapeutic strategy to combat diabetes-associated vascular pathology and its complications.

Keywords:  Exosome; Perivascular preadipocyte; Vascular remodeling

DOI:  https://doi.org/10.1016/j.ncrna.2026.01.006