bims-evecad 2026-04-19 papers

bims-evecad

Biomed News

on Extracellular vesicles and cardiovascular disease

Issue of 2026–04–19
eight papers selected by
Cliff Dominy

Extracellular Vesicles Modulation by an Adiponectin Receptor Agonist Provides Cardioprotection for Myocardial Ischemic Injury.
Small vesicles, big potential: A review of innovative exosome delivery and molecular mechanisms in preclinical myocardial infarction models.
Exosomes and Extracellular Vesicles in CAR-T Cell Therapy: Emerging Mediators and Biomarkers of Cardiac Injury.
Vascular endothelial cell-derived small extracellular vesicles: A protective role against cardiomyocyte apoptosis in ischemia-reperfusion injury through miR410-3p-modulated smad7 pathway.
The role of extracellular vesicles in cell-cell crosstalk in cardiotoxicity.
Exosomes derived from Bcl-2-engineered iPSC-cardiomyocytes mitigate aortic valve calcification and inhibit cardiomyocyte apoptosis.
Cardiac targeting extracellular vesicles combined with quercetin co-delivery system enhances the therapeutic efficacy of myocardial infarction.
Mapping the miRNA landscape of primitive macrophage extracellular vesicles highlights their pro-vasculogenic effects in engineered human cardiac tissue.

Adv Healthc Mater. 2026 Apr 14. e05837

Extracellular Vesicles Modulation by an Adiponectin Receptor Agonist Provides Cardioprotection for Myocardial Ischemic Injury.

Jialing Tang, Wing Yan Chung, Serena M Pulente, Yubin Lei, Khang Nguyen, Eddie Tam, Nadya M Morrow, Ilka Lorenzen-Schmidt, Fengxia Xiao, Augusto Zani, Dylan Burger, Hye Kyoung Sung, Erin E Mulvihill, Gary Sweeney.

  Ischemic heart disease is a leading cause of global morbidity and mortality, with more effective clinical therapies needed to mitigate cardiac ischemic injury. Extracellular vesicles (EVs) mediate intercellular communication in cardiac pathophysiology. Adiponectin mediates cardioprotective effects yet its relationship with EVs biology remains unexplored. We investigated whether ALY688, an adiponectin receptor agonist, modulates EV biogenesis and cargo to confer cardioprotection in a mouse model of myocardial infarction (MI). ALY688 (15 mg/kg daily for 28 days) significantly attenuated MI-induced cardiac dysfunction, reduced infarct size, and decreased fibrotic scar in both lean mice on standard chow and obese mice fed a high-fat diet. Plasma EVs were isolated and while MI reduced circulating EV numbers, ALY688 restored EV production and enhanced loading with bioactive adiponectin. In addition, proteomic analysis revealed ALY688-shaped EVs were enriched in metabolism regulated proteins. The direct functional effects and mechanisms of EV action were examined in iPSC-derived cardiomyocytes and H9c2 cells. EV from ALY688 treated mice (EVALY) reduced hypoxia-induced apoptosis, cell death, and ROS accumulation while restoring mitochondrial function and enhancing autophagy flux, whereas EV from control mice did not. Importantly, intervention with systemic EVALY administration to mice reduced post-MI plasma troponin I and LDH levels, decreased apoptosis, and improved mitochondrial dynamics. Thus, we show that ALY688 enhances EV-mediated cardioprotection through multiple cellular mechanisms including adiponectin delivery, oxidative stress reduction, autophagy restoration, and mitochondrial recovery. These findings provide preclinical evidence supporting the feasibility of evidence for harnessing endogenous repair mechanisms through EVs modulation to mitigate acute cardiovascular injury.

Keywords:  adiponectin; cardiac protection; extracellular vesicles; myocardial ischemia

DOI:  https://doi.org/10.1002/adhm.202505837
Animal Model Exp Med. 2026 Apr 13.

Small vesicles, big potential: A review of innovative exosome delivery and molecular mechanisms in preclinical myocardial infarction models.

Chayanisa Phutiyothin, Kovit Pattanapanyasat, Sarawut Kumphune.

  Exosomes have emerged as promising therapeutic carriers, with over 40 000 scientific publications reflecting their exponential growth in biomedical research. Cardiovascular diseases (CVDs) are the leading cause of mortality worldwide. Among these, myocardial infarction (MI) represents the most prevalent and devastating form, contributing significantly to global morbidity and mortality. Reducing the mortality and long-term complications associated with MI is therefore both necessary and urgent. Exosomes, naturally occurring extracellular vesicles, offer a promising cell-free alternative for drug delivery and cardiac repair and regeneration after ischemic injury due to their ability to transport bioactive proteins, lipids, and RNA. This narrative review summarizes recent advancements in exosome-based therapeutics for ischemic heart disease, focusing on the efficacy of various animal models. Various approaches are being studied to optimize exosome-based therapies, including methods to enhance their stability, targeting ability, and bioavailability in the cardiovascular system, highlighting the potential of exosomes not only as drug delivery vehicles but also as regenerative mediators capable of promoting myocardial repair and reducing MI. With continued advances in exosome technology and a deeper understanding of their biological functions, there is growing optimism that these vesicles could pave the way for more effective and less invasive treatments for cardiovascular diseases in the near future.

Keywords:  animal models; drug delivery; exosome; extracellular vesicle; myocardial infarction

DOI:  https://doi.org/10.1002/ame2.70199
Cardiol Rev. 2026 Apr 16.

Exosomes and Extracellular Vesicles in CAR-T Cell Therapy: Emerging Mediators and Biomarkers of Cardiac Injury.

Jatin Thukral, Pyush Moudgil, Ninaad Sindhwani, Abhay Mann, Sakshi Makkar, Jasmine Kaur, Riya Kaushal Shah, Harbir Kaur, Nikhil Thukral, Siddharth Pravin Agrawal, William H Frishman, Wilbert S Aronow.

  Chimeric antigen receptor T-cell (CAR-T) therapy has transformed outcomes in hematologic malignancies but is frequently complicated by cardiovascular toxicity, most notably in the setting of cytokine release syndrome. While systemic inflammation, endothelial activation, and myocardial stress have been implicated, the mechanistic links between immune activation and cardiac injury remain incompletely understood. Exosomes and other extracellular vesicles (EVs) have emerged as critical mediators of intercellular communication during immune responses, carrying bioactive cargo including cytokines, microRNAs, proteins, and lipids that can modulate cardiovascular function. In the context of CAR-T therapy, EVs derived from activated T-cells, tumor cells, and injured endothelium may amplify inflammatory signaling, promote endothelial dysfunction, and contribute directly to myocardial injury. Importantly, EVs are detectable in peripheral blood and exhibit dynamic changes in concentration and cargo during CAR-T-associated toxicities, positioning them as promising biomarkers for early detection, risk stratification, and prognostication of cardiac injury. This review synthesizes current evidence on the biogenesis, functional roles, and cardiovascular effects of exosomes and EVs in CAR-T therapy, highlighting their potential as mechanistic mediators and translational biomarkers. We also discuss existing knowledge gaps, technical challenges in EV characterization, and future directions for integrating EV-based diagnostics into cardio-oncology practice.

Keywords:  biomarkers; cardio-oncology; cardiotoxicity; chimeric antigen receptor T-cell therapy; cytokine release syndrome; endothelial dysfunction; exosomes; extracellular vesicles

DOI:  https://doi.org/10.1097/CRD.0000000000001246
J Int Med Res. 2026 Apr;54(4): 3000605261435745

Vascular endothelial cell-derived small extracellular vesicles: A protective role against cardiomyocyte apoptosis in ischemia-reperfusion injury through miR410-3p-modulated smad7 pathway.

Xiaoqiang Liu, Yulong Ge, Xing Xing, Junyi Liu, Hangwei Chen, Di Wang, Huaner Ni, Weifeng Li, Fang Wang.

  ObjectiveReperfusion therapy is essential for preserving cardiac tissue in patients with acute myocardial infarction. However, ischemia-reperfusion exacerbates cardiac damage. Vascular endothelial cell-derived small extracellular vesicles play a pivotal role in ischemia-reperfusion injury; although the underlying mechanisms remain poorly understood. Therefore, this study aimed to elucidate the mechanisms of vascular endothelial cell-derived small extracellular vesicles and investigate their potential therapeutic roles.MethodsSmall extracellular vesicles derived from vascular endothelial cells were isolated using ultracentrifugation, and their characteristics were confirmed using transmission electron microscopy, nanoparticle tracking analysis, and western blotting. Their effects on myocardial injury was evaluated in vivo using a mouse myocardial ischemia-reperfusion model, and their role was further examined in vitro using a cellular hypoxia/reoxygenation model. The key micro ribonucleic acid in small extracellular vesicles was screened via high-throughput sequencing, and its regulatory effect on cardiomyocyte apoptosis was verified in vitro through intervention experiments. The key gene was predicted using miRanda and TargetScan, and the related interaction was verified by a dual-luciferase reporter assay and ribonucleic acid immunoprecipitation.ResultsOur in vivo study revealed that small extracellular vesicles significantly attenuated ischemia-reperfusion-induced cardiomyocyte apoptosis and improved cardiac function. We also analyzed micro ribonucleic acid expression in small extracellular vesicles and found that miR410-3p was highly expressed and associated with cellular apoptosis. In vitro experiments demonstrated that small extracellular vesicles increased miR410-3p expression in cardiomyocytes and that miR410-3p effectively inhibited cardiomyocyte apoptosis in a cellular ischemia-reperfusion model. Conversely, miR410-3p inhibition attenuated the protective effect of small extracellular vesicles. Moreover, we found that SMAD family member 7 is one of the target messenger ribonucleic acids of miR410-3p and affects cellular apoptosis by modulating nuclear factor kappa-light-chain-enhancer of activated B cells. Cellular experiments verified that the antiapoptotic effect of miR410-3p was neutralized by SMAD family member 7 overexpression.ConclusionsThese results revealed that vascular endothelial cell-derived small extracellular vesicles attenuate ischemia-reperfusion-induced cardiomyocyte apoptosis via the miR410-3p/SMAD family member 7 axis. This study provides valuable insights into the molecular mechanisms underlying ischemia-reperfusion-induced myocardial damage and highlights potential therapeutic opportunities for mitigating it.

Keywords:  Ischemia–reperfusion injury; SMAD family member 7; cardiomyocytes apoptosis; miR410-3p; small extracellular vesicles

DOI:  https://doi.org/10.1177/03000605261435745
J Physiol. 2026 Apr 15.

The role of extracellular vesicles in cell-cell crosstalk in cardiotoxicity.

Gabriella Bachynskyj-Bilas, Debbie J Otto, Daniel Stratton, Katja Rietdorf, Daniel M Johnson, Calum J McMullen.

  Cardiotoxicity can be a result of the action of various therapeutic drugs, including anti-cancer drugs, and can pose a greater risk to patients' health than the underlying disease being treated. As cardiac function relies on the interplay between different cell types, dysfunction in cell-cell crosstalk can promote disease-associated mechanisms. Extracellular vesicles (EVs) are lipid bilayer structures that provide a means of cell-cell communication via delivery of bioactive cargo. EVs contribute to both physiology and pathophysiology, having recently been implicated in the pathogenesis of cardiovascular diseases (CVDs). Cardiotoxicity displays pathological similarities to those seen in numerous CVDs, suggesting a potential role for EVs in this process. This role has been confirmed in studies on the anti-cancer drug doxorubicin, observing that EVs generated by doxorubicin-treated cancer cells can drive cardiotoxicity in healthy cells present in the cardiovascular system. Conversely, EVs have also shown therapeutic potential in treating cardiovascular pathologies. EVs, such as those originating from stem cells, have been observed to disrupt pathogenesis of CVD and doxorubicin-induced cardiotoxicity, suggesting potential for EV-based therapeutics. As current therapeutic strategies tackling cardiotoxicity treat late-stage pathological changes and have limited long-term efficacy, therapeutics targeting mechanisms that initiate and drive cardiotoxicity may be more effective in preserving cardiac function. Overall, this review demonstrates the potential contribution of EVs in cardiovascular (patho)physiology through mediating cell-cell communication. This review aims to highlight the need for further study to fully understand the significance of EVs in driving drug-induced cardiotoxicity and includes suggestions for methods of establishing accessible EV-based therapeutics for at-risk patients.

Keywords:  cardiotoxicity; crosstalk; extracellular vesicles (EVs)

DOI:  https://doi.org/10.1113/JP289298
Int J Pharm. 2026 Apr 13. pii: S0378-5173(26)00325-X. [Epub ahead of print] 126877

Exosomes derived from Bcl-2-engineered iPSC-cardiomyocytes mitigate aortic valve calcification and inhibit cardiomyocyte apoptosis.

Ni Li, Renyuan Xiao, Linwen Zhu, Liyan Cai, Zheng Zhang, Lebo Sun, Huoshun Shi, Honghua Ye, Guofeng Shao, Jianqing Gao.

  Calcific Aortic Valve Disease (CAVD) is a progressive cardiovascular disorder, the pathological processes of which are correlated with cell apoptosis, inflammatory response, and osteogenic remodeling of valve interstitial cells. Presently, there exists no effective pharmacological treatment or intervention to impede or reverse the advancement of this disease. Systematically identifying key molecular biomarkers and their regulatory pathways is crucial for the formulation of novel therapeutic strategies. Exosomes, functioning as a novel drug delivery system, can transport specific functional molecules. In this research, proteomic and transcriptomic analyses disclosed an imbalance in the bcl2/bax apoptosis regulatory axis in CAVD. Further exploration indicated that miR-132, which IL-1β regulates, is dysregulated and associated with increased cellular apoptosis. To re-establish homeostasis in apoptotic and inflammatory pathways, engineered exosomes overexpressing bcl2, derived from induced pluripotent stem cell-derived cardiomyocytes (iPSCbcl2-CM-Exos), were constructed. In vitro experiments demonstrated that iPSCbcl2-CM-Exos significantly diminished the apoptosis rate of cardiomyocytes and valve interstitial cells induced by H2O2. Modulations in apoptosis-related markers further supported their potential anti-apoptotic effect. In vivo, iPSCbcl2-CM-Exos are safe and effective. They upregulate bcl2, downregulate bax, restore miR-132 expression, and inhibit the abnormal elevation of IL-1β, thereby notably reducing the apoptosis of valve interstitial cells, enhancing cardiac function, and alleviating leaflet thickening and fibrosis. This study identifies an imbalance in the bcl2/bax axis as a key molecular characteristic of CAVD. It demonstrates that bcl2-engineered exosomes can simultaneously target apoptotic and inflammatory pathways, thereby presenting a promising cell-free therapeutic strategy for CAVD.

Keywords:  Apoptosis; Bcl2/bax; Calcific aortic valve disease; Exosomes; IL-1β; miR-132

DOI:  https://doi.org/10.1016/j.ijpharm.2026.126877
Biomater Adv. 2026 Apr 09. pii: S2772-9508(26)00178-0. [Epub ahead of print]185 214880

Cardiac targeting extracellular vesicles combined with quercetin co-delivery system enhances the therapeutic efficacy of myocardial infarction.

Xinxin Zhang, Rui Wang, Xinpeng Li, Jiaxin Song, Yongtao Wang, Emeli Chatterjee, Guoping Li, Jizong Jiang, Jianhua Yao.

  Myocardial infarction (MI) poses a significant threat to human health. The complex pathological changes following MI involve the generation of reactive oxygen species (ROS) and inflammatory mediators that aggravate myocardial injury. Single-drug treatment strategies have proven insufficient in effectively addressing MI; therefore, targeted drugs for its prevention and treatment are still lacking. Human plasma-derived extracellular vesicles (hEV) are promising therapeutic agents and drug delivery vehicles for MI. At the same time, quercetin (QU), a natural compound with immunomodulatory and antioxidant properties, holds potential in this regard. Therefore, the combination of these two agents may enhance their therapeutic effects against MI. In this study, we developed a cardiac-targeting peptide-modified hEV loaded with QU, as a co-delivery system (CTP-hEV-QU). This system demonstrated the ability to target infarcted hearts, reduce ROS levels, promote macrophage polarization from the M1 to M2 phenotype, and inhibit apoptosis in cardiomyocytes and vascular endothelial cells. CTP-hEV-QU exhibited an enhanced capacity to repair injured hearts through mechanisms closely associated with anti-inflammatory effects, antioxidative activity, and anti-apoptosis. Our findings elucidate the synergistic therapeutic mechanism of CTP-hEV-QU in MI repair, offering valuable insights into the development of novel targeted drugs for treating MI.

Keywords:  Drug combination; Extracellular vesicle; Myocardial infarction; Quercetin; Targeted therapy

DOI:  https://doi.org/10.1016/j.bioadv.2026.214880
APL Bioeng. 2026 Jun;10(2): 026102

Mapping the miRNA landscape of primitive macrophage extracellular vesicles highlights their pro-vasculogenic effects in engineered human cardiac tissue.

Karl T Wagner, Shira Landau, Gregory M Kent, David F Bodenstein, Milica Radisic.

Resident cardiac macrophages, derived from primitive yolk sac precursors during embryogenesis, have increasingly been recognized for their distinct phenotype and functions in regulating homeostasis of the human heart. However, the profile of their extracellular vesicles (EVs) in cardiac signaling and regulation remains uncharted. Here, we employ differentiation of human pluripotent stem cell-derived primitive macrophages (Mac), harvesting their secreted EVs and performing in-depth characterization of associated microRNAs (miRNAs). Primitive macrophages secreted nanoscale EVs that expressed canonical EV markers, and miRNA sequencing highlighted a diverse and unique profile of miRNAs when compared to EVs sourced from other principal cardiac cell lineages and published data from monocyte-derived cells. In particular, we noted the abundance and enrichment of vascular-modulatory let-7 miRNAs and miR-126-3p. Functional screening of Mac-EVs in a 3D model of in vitro cardiac vasculogenesis confirmed enhanced early endothelial cell organization and branching. Establishing a reference for the human Mac-EV miRNome enables further hypothesis-driven mechanistic tests of Mac-EV miRNAs in mediating cardiac physiology and disease, opening the door to identification of therapeutic targets and modalities for cardiac repair.

DOI: https://doi.org/10.1063/5.0313731